Perinatal consumption of thiamin-fortified fish sauce in rural Cambodia: a randomized controlled efficacy trial

USDA-ARS?s Scientific Manuscript database

Importance: Infantile beriberi, a potentially fatal disease caused by thiamin deficiency, remains a public health concern in Cambodia and regions where B-vitamin poor, polished white rice is a staple food. Low maternal thiamin intake reduces breast milk thiamin concentrations, placing breastfed infa...

Massive digoxin ingestion. Report of a case and review of currently available therapies.

PubMed Central

Bremner, W F; Third, J L; Lawrie, T D

1977-01-01

Recent reports of treatment of massive digoxin overdosage have emphasized the success of medical therapy. This report describes a fatal outcome to this problem despite aggressive medical management, including pervenous cardiac pacing and draws attention to deficiencies in current treatment of a serious problem. PMID:328024

Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier.

PubMed

Vinod, K V; Hitha, B; Kaaviya, R; Dutta, T K

2015-03-01

Congenital factor X (FX) deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

Late vitamin K deficiency bleeding leading to a diagnosis of cystic fibrosis: a case report.

PubMed

Ngo, B; Van Pelt, K; Labarque, V; Van De Casseye, W; Penders, J

2011-01-01

Vitamin K deficiency bleeding (VKDB) in infants still occurs despite worldwide use of prophylaxis. Clinical manifestations can be dramatic with over 50% of patients presenting with intracranial haemorrhage and a mortality rate of 20% in late vitamin K deficiency bleeding. Special attention should be given to infants with a high risk profile (preterm, breast feeding, cholestasis, malabsorption). A tentative diagnosis can be made observing quick normalisation of some easy-to-perform haemostatic parameters (PT, aPTT) after administration of vitamin K. Nowadays, VKDB can still be the first clinical sign of diseases causing malabsorption of fat-soluble vitamins. In this case report, VKDB led to the diagnosis of cystic fibrosis, the most common fatal autosomal recessive disease among Caucasian people.

Mouse Model for Human Arginase Deficiency

PubMed Central

Iyer, Ramaswamy K.; Yoo, Paul K.; Kern, Rita M.; Rozengurt, Nora; Tsoa, Rosemarie; O'Brien, William E.; Yu, Hong; Grody, Wayne W.; Cederbaum, Stephen D.

2002-01-01

Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a disorder characterized by progressive mental impairment, growth retardation, and spasticity and punctuated by sometimes fatal episodes of hyperammonemia. We constructed a knockout mouse strain carrying a nonfunctional AI gene by homologous recombination. Arginase AI knockout mice completely lacked liver arginase (AI) activity, exhibited severe symptoms of hyperammonemia, and died between postnatal days 10 and 14. During hyperammonemic crisis, plasma ammonia levels of these mice increased >10-fold compared to those for normal animals. Livers of AI-deficient animals showed hepatocyte abnormalities, including cell swelling and inclusions. Plasma amino acid analysis showed the mean arginine level in knockouts to be approximately fourfold greater than that for the wild type and threefold greater than that for heterozygotes; the mean proline level was approximately one-third and the ornithine level was one-half of the proline and ornithine levels, respectively, for wild-type or heterozygote mice—understandable biochemical consequences of arginase deficiency. Glutamic acid, citrulline, and histidine levels were about 1.5-fold higher than those seen in the phenotypically normal animals. Concentrations of the branched-chain amino acids valine, isoleucine, and leucine were 0.4 to 0.5 times the concentrations seen in phenotypically normal animals. In summary, the AI-deficient mouse duplicates several pathobiological aspects of the human condition and should prove to be a useful model for further study of the disease mechanism(s) and to explore treatment options, such as pharmaceutical administration of sodium phenylbutyrate and/or ornithine and development of gene therapy protocols. PMID:12052859

Perinatal consumption of thiamine-fortified fish sauce in rural Cambodia. A randomized clinical trial

USDA-ARS?s Scientific Manuscript database

Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, is a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine placing breastfed infants at risk of beriberi. The objective wa...

AIDS: Are Children at Risk? ERIC Digest 16.

ERIC Educational Resources Information Center

ERIC Clearinghouse on Teacher Education, Washington, DC.

Lack of knowledge and misinformation about Acquired Immune Deficiency Syndrome (AIDS), a fatal disease with no cure or vaccine, has caused widespread public concern. Education is an effective way to reduce fears and prevent the spread of the disease. Public school personnel must have accurate information about AIDS in order to make suitable…

Red palm oil-supplemented and biofortified gari on the carotenoid and retinyl palmitate concentrations of triacylglycerol-rich plasma of women

USDA-ARS?s Scientific Manuscript database

Boiled biofortified cassava containing ß-carotene (BC) can increase retinyl palmitate (RP) in triacylglycerol (TAG)-rich plasma. Thus, it might alleviate vitamin A deficiency. Cassava requires extensive preparation to decrease its level of cyanogenic glucosides, which can be fatal. Garification ...

AIDS: Education's New Dilemma.

ERIC Educational Resources Information Center

Freeland, D. Kay; Faber, Charles F.

The acquired immune deficiency syndrome (AIDS) is an incurable, fatal disease that is caused by a virus that eventually destroys the body's immune system. While AIDS is contagious, the risk of contracting AIDS through casual contact is said to be negligible. A review of the court cases involving students with AIDS reveals that the precedent has…

Two novel mutations in thymidine kinase-2 cause early onset fatal encephalomyopathy and severe mtDNA depletion.

PubMed

Lesko, Nicole; Naess, Karin; Wibom, Rolf; Solaroli, Nicola; Nennesmo, Inger; von Döbeln, Ulrika; Karlsson, Anna; Larsson, Nils-Göran

2010-03-01

Deficiency of thymidine kinase-2 (TK2) has been described in children with early onset fatal skeletal myopathy. TK2 is a mitochondrial deoxyribonucleoside kinase required for the phosphorylation of deoxycytidine and deoxythymidine and hence is vital for the maintenance of a balanced mitochondrial dNTP pool in post-mitotic tissues. We describe a patient with two novel TK2 mutations, which caused disease onset shortly after birth and death at the age of three months. One mutation (219insCG) generated an early stop codon, thus preventing the synthesis of a functional protein. The second mutation (R130W) resulted in an amino acid substitution, which caused a severe reduction (<3%) of TK2 enzyme activity. These two novel TK2 mutations cause an extremely severe phenotype with overwhelming central nervous system symptoms not commonly seen in patients with TK2-deficiency. We conclude that the severe clinical presentation in this patient was due to a virtual lack of mitochondrial TK2 activity. Copyright 2009 Elsevier B.V. All rights reserved.

Microhemorrhage is an Early Event in the Pulmonary Fibrotic Disease of PECAM-1 Deficient FVB/n Mice

PubMed Central

Young, Lena C.; Woods, Steven J.; Groshong, Steven D.; Basaraba, Randall J.; Gilchrist, John M.; Higgins, David M.; Gonzalez-Juarrero, Mercedes; Bass, Todd A.; Muller, William A.; Schenkel, Alan R.

2014-01-01

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells. We show here that the spontaneous development of fibrotic disease in PECAM-1 deficient FVB/n mice is characterized by early loss of vascular integrity in pulmonary capillaries, resulting in spontaneous microbleeds. Hemosiderin-positive macrophages were found in interstitial spaces and bronchoalveolar lavage (BAL) fluid in relatively healthy animals. We also observed a gradually increasing presence of hemosiderin-positive macrophages and fibrin deposition in the advanced stages of disease, corresponding to the accumulation of collagen, IL-10 expression, and myofibroblasts expressing alpha smooth muscle actin (SMA). Together with the growing evidence that pulmonary microbleeds and coagulation play an active part in human pulmonary fibrosis, this data further supports our hypothesis that PECAM-1 expression is necessary for vascular barrier function control and regulation of homeostasis specifically, in the pulmonary environment. PMID:24972347

Thymic pseudotumorous enlargement due to follicular hyperplasia in a human immunodeficiency virus sero-positive patient. Immunohistochemical and molecular biological study of viral infected cells.

PubMed

Prevot, S; Audouin, J; Andre-Bougaran, J; Griffais, R; Le Tourneau, A; Fournier, J G; Diebold, J

1992-03-01

An enlargement of the thymus suggesting a tumor was discovered in a 28-year-old man who had early-stage acquired immune deficiency syndrome. A biopsy was performed. The adipose involuted thymus, with persistence of many Hassall's corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that previously described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p24 human immunodeficiency virus protein were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells), and also in many cells that may have been either lymphocytes and/or epithelial cells in the interfollicular areas. The tissue was negative for Epstein-Barr virus DNA sequences, as determined by the polymerase chain reaction. These observations identify the first state of infection of the thymus in a human immune deficiency virus-infected adult, preceding the severe involution with lymphoid depletion observed in all fatal cases of acquired immunodeficiency syndrome in which the thymus has been analyzed.

Diagnosing human blood clotting deficiency.

PubMed

Ong, Chong Cheen; Gopinath, Subash C B; Rebecca, Leong Wei Xian; Perumal, Veeradasan; Lakshmipriya, Thangavel; Saheed, Mohamed Shuaib Mohamed

2018-05-15

There are different clotting factors present in blood, carries the clotting cascade and excessive bleeding may cause a deficiency in the clotting Diagnosis of this deficiency in clotting drastically reduces the potential fatality. For enabling a sensor to detect the clotting factors, suitable probes such as antibody and aptamer have been used to capture these targets on the sensing surface. Two major clotting factors were widely studied for the diagnosis of clotting deficiency, which includes factor IX and thrombin. In addition, factor IX is considered as the substitute for heparin and the prothrombotic associated with the increased thrombin generation are taking into account their prevalence. The biosensors, surface plasmon resonance, evanescent-field-coupled waveguide-mode sensor, metal-enhanced PicoGreen fluorescence and electrochemical aptasensor were well-documented and improvements have been made for high-performance sensing. We overviewed detecting factor IX and thrombin using these biosensors, for the potential application in medical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Anaemia, iron deficiency and susceptibility to infections.

PubMed

Jonker, Femke A M; Boele van Hensbroek, Michaël

2014-11-01

Anaemia, iron deficiency and infections are three major causes of childhood morbidity and mortality throughout the world, although they predominantly occur in resource limited settings. As the three conditions may have the same underlying aetiologies, they often occur simultaneously and may interact. Being an essential component in erythropoiesis, iron is also essential for proper functioning of the host immune system as well as an essential nutrient for growth of various pathogens, including non-typhoid salmonella. This has resulted in a treatment dilemma in which iron is needed to treat the iron deficient anaemia and improve the immune system of the host (child), but the same treatment may also put the child at an increased, potentially fatal, infection risk. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Thiamine deficiency in childhood with attention to genetic causes: Survival and outcome predictors.

PubMed

Ortigoza-Escobar, Juan Darío; Alfadhel, Majid; Molero-Luis, Marta; Darin, Niklas; Spiegel, Ronen; de Coo, Irenaeus F; Gerards, Mike; Taylor, Robert W; Artuch, Rafael; Nashabat, Marwan; Rodríguez-Pombo, Pilar; Tabarki, Brahim; Pérez-Dueñas, Belén

2017-09-01

Primary and secondary conditions leading to thiamine deficiency have overlapping features in children, presenting with acute episodes of encephalopathy, bilateral symmetric brain lesions, and high excretion of organic acids that are specific of thiamine-dependent mitochondrial enzymes, mainly lactate, alpha-ketoglutarate, and branched chain keto-acids. Undiagnosed and untreated thiamine deficiencies are often fatal or lead to severe sequelae. Herein, we describe the clinical and genetic characterization of 79 patients with inherited thiamine defects causing encephalopathy in childhood, identifying outcome predictors in patients with pathogenic SLC19A3 variants, the most common genetic etiology. We propose diagnostic criteria that will aid clinicians to establish a faster and accurate diagnosis so that early vitamin supplementation is considered. Ann Neurol 2017;82:317-330. © 2017 American Neurological Association.

Exploring Self-Efficacy and Locus of Control as Risk Factors in Sexual Decision Making for African American Women

ERIC Educational Resources Information Center

Pimpleton, Asher M.

2012-01-01

Sexually transmitted diseases have reached epidemic proportions, especially among African Americans. However, African American women have emerged as being one of the hardest hit groups by the most fatal of sexually transmitted diseases--the Human Immunodeficiency Virus (HIV) and the Acquired Immune Deficiency Syndrome (AIDS). Although there has…

LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.

PubMed

Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A

2011-03-01

The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (p<0.005) were hyperglycaemia, hepatic cytolysis, and altered consciousness at admission. Compared to a group of SURF1-deficient Leigh syndrome patients assembled from the literature, SLSJ-COX is distinct by the occurrence of metabolic crises, leading to earlier and higher mortality (p=0.001). SLSJ-COX is clinically distinct, with acute fatal acidotic crises on a backdrop of chronic moderate developmental delay and hyperlactataemia. Leigh syndrome is common. Stroke-like episodes can occur. The Leigh syndrome of SLSJ-COX differs from that of SURF1-related COX deficiency. SLSJ-COX has a different spectrum of associated abnormalities, acidotic crises being particularly suggestive of LRPPRC related Leigh syndrome. Even among A354V homozygotes, pronounced differences in survival and severity occur, showing that other genetic and/or environmental factors can influence outcome.

Hereditary properdin deficiency in three families of Tunisian Jews.

PubMed

Schlesinger, M; Mashal, U; Levy, J; Fishelson, Z

1993-09-01

Hereditary properdin deficiency is a rare genetic disorder of the complement system. Three propositi and six additional family members with properdin deficiency have been found following analysis of the hemolytic activity of the classical (CH50) and the alternative (AP50) complement pathways in the sera of 101 survivors of meningococcal infections and 59 survivors of severe pneumococcal and Haemophilus influenza infections. All the properdin-deficient individuals had undetectable levels of properdin by radial immunodiffusion and by Western blotting. They belonged to three non-related families of Tunisian Jews who came from different parts of Tunisia. Two patients had a meningococcal infection at 15 and 16 years of age, respectively, and one had Haemophilus influenza meningitis at 1.5 years of age. In contrast to the fulminant and fatal course of meningococcal infection which was previously described in some properdin-deficient patients, our patients had a relatively mild disease. Properdin deficiency may not be as rare as previously thought. Analysis of AP50, in addition to CH50, in sera of patients who had meningococcal infection, will probably disclose many more cases of hereditary properdin deficiency. In addition, our findings indicate that, as in other complement abnormalities, hereditary properdin deficiency may also be associated with the ethnic origin of the patient.

Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: acrodermatitis enteropathica and transient neonatal zinc deficiency as examples.

PubMed

Kasana, Shakhenabat; Din, Jamila; Maret, Wolfgang

2015-01-01

Discovering genetic causes of zinc deficiency has been a remarkable scientific journey. It started with the description of a rare skin disease, its treatment with various agents, the successful therapy with zinc, and the identification of mutations in a zinc transporter causing the disease. The journey continues with defining the molecular and cellular pathways that lead to the symptoms caused by zinc deficiency. Remarkably, at least two zinc transporters from separate protein families are now known to be involved in the genetics of zinc deficiency. One is ZIP4, which is involved in intestinal zinc uptake. Its mutations can cause acrodermatitis enteropathica (AE) with autosomal recessive inheritance. The other one is ZnT2, the transporter responsible for supplying human milk with zinc. Mutations in this transporter cause transient neonatal zinc deficiency (TNZD) with symptoms similar to AE but with autosomal dominant inheritance. The two diseases can be distinguished in affected infants. AE is fatal if zinc is not supplied to the infant after weaning, whereas TNZD is a genetic defect of the mother limiting the supply of zinc in the milk, and therefore the infant usually will obtain enough zinc once weaned. Although these diseases are relatively rare, the full functional consequences of the numerous mutations in ZIP4 and ZnT2 and their interactions with dietary zinc are not known. In particular, it remains unexplored whether some mutations cause milder disease phenotypes or increase the risk for other diseases if dietary zinc requirements are not met or exceeded. Thus, it is not known whether widespread zinc deficiency in human populations is based primarily on a nutritional deficiency or determined by genetic factors as well. This consideration becomes even more significant with regard to mutations in the other 22 human zinc transporters, where associations with a range of diseases, including diabetes, heart disease, and mental illnesses have been observed. Therefore, clinical tests for genetic disorders of zinc metabolism need to be developed.

Jane Austen's lifelong health problems and final illness: New evidence points to a fatal Hodgkin's disease and excludes the widely accepted Addison's.

PubMed

Upfal, A

2005-06-01

Jane Austen is typically described as having excellent health until the age of 40 and the onset of a mysterious and fatal illness, initially identified by Sir Zachary Cope in 1964 as Addison's disease. Her biographers, deceived both by Cassandra Austen's destruction of letters containing medical detail, and the cheerful high spirits of the existing letters, have seriously underestimated the extent to which illness affected Austen's life. A medical history reveals that she was particularly susceptible to infection, and suffered unusually severe infective illnesses, as well as a chronic conjunctivitis that impeded her ability to write. There is evidence that Austen was already suffering from an immune deficiency and fatal lymphoma in January 1813, when her second and most popular novel, Pride and Prejudice, was published. Four more novels would follow, written or revised in the shadow of her increasing illness and debility. Whilst it is impossible now to conclusively establish the cause of her death, the existing medical evidence tends to exclude Addison's disease, and suggests there is a high possibility that Jane Austen's fatal illness was Hodgkin's disease, a form of lymphoma.

Review on Vitamin K Deficiency and its Biomarkers: Focus on the Novel Application of PIVKA-II in Clinical Practice.

PubMed

Dong, Rui; Wang, Nianyue; Yang, Yongfeng; Ma, Li; Du, Qiang; Zhang, Wei; Tran, Anh H; Jung, Haiyoung; Soh, Andrew; Zheng, Yijie; Zheng, Shan

2018-04-01

Vitamin K (VK) is a co-factor of the γ-glutamyl carboxylase that catalyzes the conversion of glutamate residues to γ-carboxyglutamate in VK-dependent proteins. The carboxylation reaction imparts the essential calcium-binding residues for the biological function of several proteins involved in the process of coagulation and bone metabolism. VK deficiency is frequently encountered in newborns and can lead to fatal hemorrhagic complications. This review describes and discusses the clinical application of VK deficiency testing. References and data were researched in PubMed and reviewed. In adults, VK deficiency is associated with uncontrolled bleeding, liver dysfunction, osteoporosis, and coronary diseases. An improved understanding of the role of VK deficiency in health and illness can be achieved by setting a gold-standard in the inter-laboratory estimations of VK. However, conventional methods used to measure the VK deficiency based upon the coagulation time lack sensitivity and specificity. Recently, the alterations in proteins induced by VK absence or antagonism (PIVKA) have proven to be suitable biomarkers for detecting VK deficiency. The measurement of PIVKA-II exhibits an enhanced sensitivity and specificity in comparison to other methods conventionally used for the assessment of VK deficiency in newborns and adults. PIVKA-II could potentially be employed as an effective biomarker in the diagnosis of VK deficiency.

Spectrum of disease outcomes in mice infected with YFV-17D

PubMed Central

Erickson, Andrea K.

2015-01-01

The host and viral factors that influence disease outcome during flavivirus infections are not fully understood. Using the live attenuated yellow fever virus (YFV) vaccine strain 17D as a model system we evaluated how viral dose, inoculation route and immunopathogenesis contributed to disease outcome in mice deficient in the type I IFN response. We found that YFV-17D infection of IFN-α/β receptor knockout mice resulted in three distinct disease outcomes: no clinical signs of disease, fatal viscerotropic disease or fatal neurotropic disease. Interestingly, viral load at disease onset did not correlate with disease outcome. However, we found increased immune infiltrates in the brain tissues of mice that developed neurotropic disease. Additionally, mice that developed viscerotropic disease, as characterized by liver and spleen pathology and/or intestinal haemorrhage, had significantly elevated levels of alanine aminotransferase, monocyte chemotactic protein and IFN-inducible protein (IP)-10 as compared with mice with no clinical signs of disease or neurotropic disease. Furthermore, mice treated with recombinant IP-10 throughout YFV-17D infection showed increased mortality and an increased percentage of mice with viscerotropic disease. Our results demonstrated that viral load did not correlate with pathogenesis, and the host immune response played a pivotal role in disease outcome and contributed to YFV-17D pathogenesis in mice. PMID:25646269

Spectrum of disease outcomes in mice infected with YFV-17D.

PubMed

Erickson, Andrea K; Pfeiffer, Julie K

2015-06-01

The host and viral factors that influence disease outcome during flavivirus infections are not fully understood. Using the live attenuated yellow fever virus (YFV) vaccine strain 17D as a model system we evaluated how viral dose, inoculation route and immunopathogenesis contributed to disease outcome in mice deficient in the type I IFN response. We found that YFV-17D infection of IFN-α/β receptor knockout mice resulted in three distinct disease outcomes: no clinical signs of disease, fatal viscerotropic disease or fatal neurotropic disease. Interestingly, viral load at disease onset did not correlate with disease outcome. However, we found increased immune infiltrates in the brain tissues of mice that developed neurotropic disease. Additionally, mice that developed viscerotropic disease, as characterized by liver and spleen pathology and/or intestinal haemorrhage, had significantly elevated levels of alanine aminotransferase, monocyte chemotactic protein and IFN-inducible protein (IP)-10 as compared with mice with no clinical signs of disease or neurotropic disease. Furthermore, mice treated with recombinant IP-10 throughout YFV-17D infection showed increased mortality and an increased percentage of mice with viscerotropic disease. Our results demonstrated that viral load did not correlate with pathogenesis, and the host immune response played a pivotal role in disease outcome and contributed to YFV-17D pathogenesis in mice. © 2015 The Authors.

GM2 Gangliosidosis Variant 0 (Sandhoff Disease) in a Mixed-Breed Dog.

PubMed

Kohyama, Moeko; Yabuki, Akira; Kawasaki, Yasuaki; Kawaguchi, Hiroaki; Miura, Naoki; Kitano, Yoshiaki; Onitsuka, Toshinori; Rahman, Mohammad Mahbubur; Miyoshi, Noriaki; Yamato, Osamu

2015-01-01

GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive, neurodegenerative lysosomal storage disease caused by simultaneous deficiencies of acid β-hexosaminidases A and B. Canine SD has so far been identified only in two purebreeds. In this article, we present the case of a 10 mo old, male dog of mixed breed that developed progressive neurological signs including ataxia, postural deficit, and visual deficits and finally died at the age of 21 mo. The dog was diagnosed with SD on the basis of the results of biochemical and histopathological analyses. This is the third report of canine SD and the first time it has been identified in a mixed breed.

In pursuit of excellence: an integrated care pathway for C1 inhibitor deficiency

PubMed Central

Manson, A L; Price, A; Dempster, J; Clinton-Tarestad, P; Greening, C; Enti, R; Hill, S; Grigoriadou, S; Buckland, M S; Longhurst, H J

2013-01-01

There are estimated to be approximately 1500 people in the United Kingdom with C1 inhibitor (C1INH) deficiency. At BartsHealth National Health Service (NHS) Trust we manage 133 patients with this condition and we believe that this represents one of the largest cohorts in the United Kingdom. C1INH deficiency may be hereditary or acquired. It is characterized by unpredictable episodic swellings, which may affect any part of the body, but are potentially fatal if they involve the larynx and cause significant morbidity if they involve the viscera. The last few years have seen a revolution in the treatment options that are available for C1 inhibitor deficiency. However, this occurs at a time when there are increased spending restraints in the NHS and the commissioning structure is being overhauled. Integrated care pathways (ICP) are a tool for disseminating best practice, for facilitating clinical audit, enabling multi-disciplinary working and for reducing health-care costs. Here we present an ICP for managing C1 inhibitor deficiency. PMID:23607500

[Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State].

PubMed

Schumann, Christina; Faust, Michael

2018-03-01

 Diabetic ketoacidosis and the hyperosmolar hyperglycemic state are the most serious diabetic emergencies. Before the discovery of insulin in 1921 by Banting and Best the diagnosis of type 1 diabetes was fatal ending in diabetic ketoacidosis equivalent to a torturous death. Today, mortality from diabetic ketoacidosis is low at approximately 2 %. But each death from these two acute metabolic complications of diabetes is potentially avoidable by improved patient and healthcare professional education. Therefore, there is a need to raise awareness of hyperglycemic crisis and its management amongst physicians.  Insulin deficiency or resistence and increased concentrations of counterreulatory hormones (glucagon, catecholamines, cortisol and growth hormone) are responsible for the development of diabetic ketoacidosis and the hyperosmolar hyperglycemic state. Hyperglycemia develops as a result of increased gluconeogenesis and accelerated glyconeogenesis. In DKA, the absolute insulin deficiency additionally leads to increased lipolysis and production of ketone bodies and resulting metabolic acidosis.  Both DKA and HHS require prompt recognition and management. The diagnosis can be suspected by clinical features and confirmed by laboratory findings.  The treatment of DKA and HHS is similar, including correction of fluid and electrolyte abnormalities and the administration of insulin. © Georg Thieme Verlag KG Stuttgart · New York.

RED CELL GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY--A NEWLY RECOGNIZED CAUSE OF NEONATAL JAUNDICE AND KERNICTERUS IN CANADA.

PubMed

NAIMAN, J L; KOSOY, M H

1964-12-12

Seven male newborns of Chinese, Greek and Italian origin presented with severe hemolytic jaundice due to red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. In five, the hemolysis was precipitated by inhalation of mothball vapours in the home. Kernicterus was evident upon admission in six infants and was fatal in four of these.G-6-PD deficiency should be suspected as a cause of jaundice in all full-term male infants of these ethnic groups. The diagnosis can be confirmed in any hospital by the methemoglobin reduction test. In areas similar to Toronto, Canada, where these high-risk ethnic groups prevail, the following measures are recommended: (1) detection of G-6-PD deficient newborns by screening cord bloods of all infants of these ethnic groups; (2) protection of affected infants from potentially hemolytic agents such as naphthalene, certain vitamin K preparations, and sulfonamides; and (3) observation of serum bilirubin levels to assess the need for exchange transfusion for hyperbilirubinemia.

Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

PubMed

Thurlow, Vanessa R; Asafu-Adjaye, Michelle; Agalou, Stamatina; Rahman, Yusof

2010-05-01

There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress.

PubMed

Xu, Jing; Pan, Shengchi; Gan, Fang; Hao, Shu; Liu, Dandan; Xu, Haibin; Huang, Kehe

2018-04-01

Keshan disease is a potentially fatal cardiomyopathy in humans. Selenium deficiency, T-2 toxin, and myocarditis virus are thought to be the major factors contributing to Keshan disease. But the relationship among these three factors is poorly described. This study aims to explore whether selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury and its underlying mechanism. Cardiomyocytes were isolated from neonatal rat and cultured at the physiological (2.0 μM) or lower concentrations of selenium with different concentrations of T-2 toxin. Our results showed that selenium deficiencies aggravated T-2 toxin-induced cardiomyocyte injury in a concentration-dependent manner as demonstrated by MTT bioassay, LDH activity, reactive oxygen species levels and caspase 3 protein expressions. T-2 toxin treatment significantly increased mRNA expressions for stress proteins GRP78 and CHOP in cardiomyocytes compared with the control. Selenium deficiencies further promoted GRP78, CHOP and p-eIF2α expressions. Knockdown of CHOP by the specific small interfering RNA eliminated the effect of selenium deficiencies on T-2 toxin-induced injury. It could be concluded that selenium deficiency aggravates T-2 toxin-induced cardiomyocyte injury through initiating more aggressive endoplasmic reticulum stress. Copyright © 2018 Elsevier B.V. All rights reserved.

Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report.

PubMed

Alameri, Majid; Shakra, Mustafa; Alsaadi, Taoufik

2015-11-23

Unexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood. We report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.

PubMed

Saada, Ann; Shaag, Avraham; Elpeleg, Orly

2003-05-01

Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.

Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies

PubMed Central

Smits, Paulien; Smeitink, Jan; van den Heuvel, Lambert

2010-01-01

Mitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders. PMID:20396601

Primary Immune Deficiencies – Principles of Care

PubMed Central

Chapel, Helen; Prevot, Johan; Gaspar, Hubert Bobby; Español, Teresa; Bonilla, Francisco A.; Solis, Leire; Drabwell, Josina

2014-01-01

Primary immune deficiencies (PIDs) are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components, mainly cells and proteins. Once recognized, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious, or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness or facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialized centers, the importance of registries, the need for multinational research, the role of patient organizations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin therapies and hematopoietic stem cell transplantation, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients worldwide have access to appropriate and sustainable medical and support services. PMID:25566243

Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation.

PubMed

Dorado, Beatriz; Area, Estela; Akman, Hasan O; Hirano, Michio

2011-01-01

Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2-/-). Although normal until postnatal day 8, Tk2-/- mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in the second week of life, while Tk1 activity decreases significantly between postnatal days 8 and 13. The down-regulation of Tk1 activity unmasks Tk2 deficiency in Tk2-/- mice and correlates with the onset of mtDNA depletion in the brain and the heart. Resistance to pathology in Tk2 mutant organs depends on compensatory mechanisms to the reduced mtDNA level. Our analyses at postnatal day 13 have revealed that Tk2-/- heart significantly increases mitochondrial transcript levels relative to the mtDNA content. This transcriptional compensation allows the heart to maintain normal levels of mtDNA-encoded proteins. The up-regulation in mitochondrial transcripts is not due to increased expression of the master mitochondrial biogenesis regulators peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and nuclear respiratory factors 1 and 2, or to enhanced expression of the mitochondrial transcription factors A, B1 or B2. Instead, Tk2-/- heart compensates for mtDNA depletion by down-regulating the expression of the mitochondrial transcriptional terminator transcription factor 3 (MTERF3). Understanding the molecular mechanisms that allow Tk2 mutant organs to be spared may help design therapies for Tk2 deficiency.

Onset and organ specificity of Tk2 deficiency depends on Tk1 down-regulation and transcriptional compensation

PubMed Central

Dorado, Beatriz; Area, Estela; Akman, Hasan O.; Hirano, Michio

2011-01-01

Deficiency of thymidine kinase 2 (TK2) is a frequent cause of isolated myopathy or encephalomyopathy in children with mitochondrial DNA (mtDNA) depletion. To determine the bases of disease onset, organ specificity and severity of TK2 deficiency, we have carefully characterized Tk2 H126N knockin mice (Tk2−/−). Although normal until postnatal day 8, Tk2−/− mice rapidly develop fatal encephalomyopathy between postnatal days 10 and 13. We have observed that wild-type Tk2 activity is constant in the second week of life, while Tk1 activity decreases significantly between postnatal days 8 and 13. The down-regulation of Tk1 activity unmasks Tk2 deficiency in Tk2−/− mice and correlates with the onset of mtDNA depletion in the brain and the heart. Resistance to pathology in Tk2 mutant organs depends on compensatory mechanisms to the reduced mtDNA level. Our analyses at postnatal day 13 have revealed that Tk2−/− heart significantly increases mitochondrial transcript levels relative to the mtDNA content. This transcriptional compensation allows the heart to maintain normal levels of mtDNA-encoded proteins. The up-regulation in mitochondrial transcripts is not due to increased expression of the master mitochondrial biogenesis regulators peroxisome proliferator-activated receptor-gamma coactivator 1 alpha and nuclear respiratory factors 1 and 2, or to enhanced expression of the mitochondrial transcription factors A, B1 or B2. Instead, Tk2−/− heart compensates for mtDNA depletion by down-regulating the expression of the mitochondrial transcriptional terminator transcription factor 3 (MTERF3). Understanding the molecular mechanisms that allow Tk2 mutant organs to be spared may help design therapies for Tk2 deficiency. PMID:20940150

A pathogenic S250F missense mutation results in a mouse model of mild aromatic l-amino acid decarboxylase (AADC) deficiency.

PubMed

Caine, Charlotte; Shohat, Meytal; Kim, Jeong-Ki; Nakanishi, Koki; Homma, Shunichi; Mosharov, Eugene V; Monani, Umrao R

2017-11-15

Homozygous mutations in the aromatic l-amino acid decarboxylase (AADC) gene result in a severe depletion of its namesake protein, triggering a debilitating and often fatal form of infantile Parkinsonism known as AADC deficiency. AADC deficient patients fail to produce normal levels of the monoamine neurotransmitters dopamine and serotonin, and suffer a multi-systemic disorder characterized by movement abnormalities, developmental delay and autonomic dysfunction; an absolute loss of dopamine is generally considered incompatible with life. There is no optimal treatment for AADC deficiency and few truly good models in which to investigate disease mechanisms or develop and refine therapeutic strategies. In this study, we introduced a relatively frequently reported but mildly pathogenic S250F missense mutation into the murine Aadc gene. We show that mutants homozygous for the mutation are viable and express a stable but minimally active form of the AADC protein. Although the low enzymatic activity of the protein resulted in only modestly reduced concentrations of brain dopamine, serotonin levels were markedly diminished, and this perturbed behavior as well as autonomic function in mutant mice. Still, we found no evidence of morphologic abnormalities of the dopaminergic cells in mutant brains. The striatum as well as substantia nigra appeared normal and no loss of dopamine expressing cells in the latter was detected. We conclude that even minute levels of active AADC are sufficient to allow for substantial amounts of dopamine to be produced in model mice harboring the S250F mutation. Such mutants represent a novel, mild model of human AADC deficiency. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vitamin E Inhibits Abdominal Aortic Aneurysm Formation in Angiotensin II–Infused Apolipoprotein E–Deficient Mice

PubMed Central

Gavrila, Dan; Li, Wei Gen; McCormick, Michael L.; Thomas, Manesh; Daugherty, Alan; Cassis, Lisa A.; Miller, Francis J.; Oberley, Larry W.; Dellsperger, Kevin C.; Weintraub, Neal L.

2014-01-01

Background Abdominal aortic aneurysms (AAAs) in humans are associated with locally increased oxidative stress and activity of NADPH oxidase. We investigated the hypothesis that vitamin E, an antioxidant with documented efficacy in mice, can attenuate AAA formation during angiotensin II (Ang II) infusion in apolipoprotein E–deficient mice. Methods and Results Six-month-old male apolipoprotein E–deficient mice were infused with Ang II at 1000 ng/kg per minute for 4 weeks via osmotic minipumps while consuming either a regular diet or a diet enriched with vitamin E (2 IU/g of diet). After 4 weeks, abdominal aortic weight and maximal diameter were determined, and aortic tissues were sectioned and examined using biochemical and histological techniques. Vitamin E attenuated formation of AAA, decreasing maximal aortic diameter by 24% and abdominal aortic weight by 34% (P<0.05, respectively). Importantly, animals treated with vitamin E showed a 44% reduction in the combined end point of fatal+nonfatal aortic rupture (P<0.05). Vitamin E also decreased aortic 8-isoprostane content (a marker of oxidative stress) and reduced both aortic macrophage infiltration and osteopontin expression (P<0.05, respectively). Vitamin E treatment had no significant effect on the extent of aortic root atherosclerosis, activation of matrix metalloproteinases 2 or 9, serum lipid profile, or systolic blood pressure. Conclusions Vitamin E ameliorates AAAs and reduces the combined end point of fatal+nonfatal aortic rupture in this animal model. These findings are consistent with the concept that oxidative stress plays a pivotal role in Ang II–driven AAA formation in hyperlipidemic mice. PMID:15933246

Exposure of unsuspecting workers to deadly atmospheres in below-ground confined spaces and investigation of related whole-air sample composition using adsorption gas chromatography.

PubMed

Smith, Philip A; Lockhart, Bonnie; Besser, Brett W; Michalski, Michael A R

2014-01-01

Hazardous atmospheres in confined spaces may be obvious when a source of air contamination or oxygen (O2) deficiency is recognized. Such is often the case in general industry settings, especially with work processes which create hazardous atmospheres that may be anticipated. Hazards present in active sewers are also well recognized; but the possibility that O2 deficiency or high airborne contaminant concentrations may exist in new construction sewers or storm drains has been repeatedly ignored with deadly results. Low O2 and high carbon dioxide (CO2) concentrations may exist in new construction manholes that have not yet been connected to an active sewer or drain system, and these concentrations have been shown to vary over time. A recent incident is described where workers repeatedly entered such a confined space without incident, but subsequent entry resulted in a fatality and a near-miss for a co-worker rescuer. Additional cases are discussed, with an emphasis placed on elevated CO2 concentrations as a causative factor. A description is provided for the adsorptive gas chromatography whole-air analysis methodology used to quantitatively determine atmospheric conditions present at this type of fatality site or others after an incident, and for the gas chromatography-mass spectrometry method used to provide confirmation of analyte identity with high certainty. Many types of confined spaces may be encountered in addition to the underground varieties discussed, and many possible atmospheric hazards are possible. The definitive whole-air analysis approach described here may be of use and should be considered to investigate many confined space fatality and near-miss cases, and to better understand the causes of dangerous atmosphere conditions that may arise in confined spaces.

Hepatic Scavenger Receptor BI Protects Against Polymicrobial-induced Sepsis through Promoting LPS Clearance in Mice*

PubMed Central

Guo, Ling; Zheng, Zhong; Ai, Junting; Huang, Bin; Li, Xiang-An

2014-01-01

Recent studies revealed that scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. However, the mechanisms underlying this protection remain largely unknown. In this study, using Scarb1I179N mice, a mouse model specifically deficient in hepatic SR-BI, we report that hepatic SR-BI protects against cecal ligation and puncture (CLP)-induced sepsis as shown by 75% fatality in Scarb1I179N mice, but only 21% fatality in C57BL/6J control mice. The increase in fatality in Scarb1I179N mice was associated with an exacerbated inflammatory cytokine production. Further study demonstrated that hepatic SR-BI exerts its protection against sepsis through its role in promoting LPS clearance without affecting the inflammatory response in macrophages, the glucocorticoid production in adrenal glands, the leukocyte recruitment to peritoneum or the bacterial clearance in liver. Our findings reveal hepatic SR-BI as a critical protective factor in sepsis and point out that promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis. PMID:24719333

Non-Hemagglutinating Flaviviruses: Molecular Mechanisms for the Emergence of New Strains via Adaptation to European Ticks

PubMed Central

Khasnatinov, Maxim A.; Ustanikova, Katarina; Frolova, Tatiana V.; Pogodina, Vanda V.; Bochkova, Nadezshda G.; Levina, Ludmila S.; Slovak, Mirko; Kazimirova, Maria; Labuda, Milan; Klempa, Boris; Eleckova, Elena; Gould, Ernest A.; Gritsun, Tamara S.

2009-01-01

Tick-borne encephalitis virus (TBEV) causes human epidemics across Eurasia. Clinical manifestations range from inapparent infections and fevers to fatal encephalitis but the factors that determine disease severity are currently undefined. TBEV is characteristically a hemagglutinating (HA) virus; the ability to agglutinate erythrocytes tentatively reflects virion receptor/fusion activity. However, for the past few years many atypical HA-deficient strains have been isolated from patients and also from the natural European host tick, Ixodes persulcatus. By analysing the sequences of HA-deficient strains we have identified 3 unique amino acid substitutions (D67G, E122G or D277A) in the envelope protein, each of which increases the net charge and hydrophobicity of the virion surface. Therefore, we genetically engineered virus mutants each containing one of these 3 substitutions; they all exhibited HA-deficiency. Unexpectedly, each genetically modified non-HA virus demonstrated increased TBEV reproduction in feeding Ixodes ricinus, not the recognised tick host for these strains. Moreover, virus transmission efficiency between infected and uninfected ticks co-feeding on mice was also intensified by each substitution. Retrospectively, the mutation D67G was identified in viruses isolated from patients with encephalitis. We propose that the emergence of atypical Siberian HA-deficient TBEV strains in Europe is linked to their molecular adaptation to local ticks. This process appears to be driven by the selection of single mutations that change the virion surface thus enhancing receptor/fusion function essential for TBEV entry into the unfamiliar tick species. As the consequence of this adaptive mutagenesis, some of these mutations also appear to enhance the ability of TBEV to cross the human blood-brain barrier, a likely explanation for fatal encephalitis. Future research will reveal if these emerging Siberian TBEV strains continue to disperse westwards across Europe by adaptation to the indigenous tick species and if they are associated with severe forms of TBE. PMID:19802385

Type-1 angiotensin receptor signaling in central nervous system myeloid cells is pathogenic during fatal alphavirus encephalitis in mice.

PubMed

Blakely, Pennelope K; Huber, Amanda K; Irani, David N

2016-08-25

Alphaviruses can cause fatal encephalitis in humans. Natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. Central nervous system (CNS) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. We investigated whether reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity within the CNS contributes to fatal alphavirus encephalitis in mice. Infected animals were treated systemically with the angiotensin receptor-blocking drug, telmisartan, given its ability to cross the blood-brain barrier, selectively block type-1 angiotensin receptors (AT1R), and inhibit Nox-derived ROS production in vascular smooth muscle and other extraneural tissues. Clinical, virological, biochemical, and histopathological outcomes were followed over time. The importance of the angiotensin II (Ang II)/AT1R axis in disease pathogenesis was confirmed by demonstrating increased Ang II levels in the CNS following infection, enhanced disease survival when CNS Ang II production was suppressed, increased AT1R expression on microglia and tissue-infiltrating myeloid cells, and enhanced disease survival in AT1R-deficient mice compared to wild-type (WT) controls. Systemic administration of telmisartan protected WT mice from lethal encephalitis caused by two different alphaviruses in a dose-dependent manner without altering virus replication or exerting any anti-inflammatory effects in the CNS. Infection triggered up-regulation of multiple Nox subunits in the CNS, while drug treatment inhibited local Nox activity, ROS production, and oxidative neuronal damage. Telmisartan proved ineffective in Nox-deficient mice, demonstrating that this enzyme is its main target in this experimental setting. Nox-derived ROS, likely arising from CNS myeloid cells triggered by AT1R signaling, are pathogenic during fatal alphavirus encephalitis in mice. Systemically administered telmisartan at non-hypotensive doses targets Nox activity in the CNS to exert a neuroprotective effect. Disruption of this pathway may have broader implications for the treatment of related infections as well as for other CNS diseases driven by oxidative injury.

Commensal Microbiota Contributes to Chronic Endocarditis in TAX1BP1 Deficient Mice

PubMed Central

Nakano, Satoko; Ikebe, Emi; Tsukamoto, Yoshiyuki; Wang, Yan; Matsumoto, Takashi; Mitsui, Takahiro; Yahiro, Takaaki; Inoue, Kunimitsu; Kawazato, Hiroaki; Yasuda, Aiko; Ito, Kanako; Yokoyama, Shigeo; Takahashi, Naohiko; Hori, Mitsuo; Shimada, Tatsuo; Moriyama, Masatsugu; Kubota, Toshiaki; Ono, Katsushige; Fujibuchi, Wataru; Jeang, Kuan-Teh; Iha, Hidekatsu; Nishizono, Akira

2013-01-01

Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-κB by editing the ubiquitylation of target molecules by its catalytic partner A20. Genetically engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory constitutions in multiple organs manifested as valvulitis or dermatitis and succumb to premature death. Laser capture dissection and gene expression microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old) revealed 588 gene transcription alterations from the wild type. SAA3 (serum amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122- and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold reduction. Intense Saa3 staining and significant I-κBα reduction were reconfirmed and massive infiltration of inflammatory lymphocytes and edema formation were seen in the area. Antibiotics-induced ‘germ free’ status or the additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's inflammatory lesions. These pathological conditions, as we named ‘pseudo-infective endocarditis’ were boosted by the commensal microbiota who are usually harmless by their nature. This experimental outcome raises a novel mechanistic linkage between endothelial inflammation caused by the ubiquitin remodeling immune regulators and fatal cardiac dysfunction. PMID:24086273

[Rhabdomyolysis - may it be a metabolic myopathy? Case report and diagnostic algorithm].

PubMed

Sebők, Ágnes; Pál, Endre; Molnár, Gergő Attila; Wittmann, István; Berenténé Bene, Judit; Melegh, Béla; Komoly, Sámuel; Hidvégi, Tibor; Balogh, Lídia; Szabó, Attila; Zsidegh, Petra

2017-11-01

We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient's age. Orv Hetil. 2017; 158(46): 1873-1882.

The genotypic and phenotypic spectrum of MTO1 deficiency.

PubMed

O'Byrne, James J; Tarailo-Graovac, Maja; Ghani, Aisha; Champion, Michael; Deshpande, Charu; Dursun, Ali; Ozgul, Riza K; Freisinger, Peter; Garber, Ian; Haack, Tobias B; Horvath, Rita; Barić, Ivo; Husain, Ralf A; Kluijtmans, Leo A J; Kotzaeridou, Urania; Morris, Andrew A; Ross, Colin J; Santra, Saikat; Smeitink, Jan; Tarnopolsky, Mark; Wortmann, Saskia B; Mayr, Johannes A; Brunner-Krainz, Michaela; Prokisch, Holger; Wasserman, Wyeth W; Wevers, Ron A; Engelke, Udo F; Rodenburg, Richard J; Ting, Teck Wah; McFarland, Robert; Taylor, Robert W; Salvarinova, Ramona; van Karnebeek, Clara D M

2018-01-01

Mitochondrial diseases, a group of multi-systemic disorders often characterized by tissue-specific phenotypes, are usually progressive and fatal disorders resulting from defects in oxidative phosphorylation. MTO1 (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved protein expressed in high-energy demand tissues has been linked to human early-onset combined oxidative phosphorylation deficiency associated with hypertrophic cardiomyopathy, often referred to as combined oxidative phosphorylation deficiency-10 (COXPD10). Thirty five cases of MTO1 deficiency were identified and reviewed through international collaboration. The cases of two female siblings, who presented at 1 and 2years of life with seizures, global developmental delay, hypotonia, elevated lactate and complex I and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in detail. For the description of phenotypic features, the denominator varies as the literature was insufficient to allow for complete ascertainment of all data for the 35 cases. An extensive review of all known MTO1 deficiency cases revealed the most common features at presentation to be lactic acidosis (LA) (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and 27/34 (79%) of patients with MTO1 deficiency, respectively; with global developmental delay/intellectual disability present in 28/29 (97%), feeding difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35 (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19 different pathogenic MTO1 variants identified in these 35 cases: one splice-site, 3 frameshift and 15 missense variants. None have bi-allelic variants that completely inactivate MTO1; however, patients where one variant is truncating (i.e. frameshift) while the second one is a missense appear to have a more severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is not viable. A ketogenic diet may have exerted a favourable effect on seizures in 2/5 patients. MTO1 deficiency is lethal in some but not all cases, and a genotype-phenotype relation is suggested. Aside from lactic acidosis and cardiomyopathy, developmental delay and other phenotypic features affecting multiple organ systems are often present in these patients, suggesting a broader spectrum than hitherto reported. The diagnosis should be suspected on clinical features and the presence of markers of mitochondrial dysfunction in body fluids, especially low residual complex I, III and IV activity in muscle. Molecular confirmation is required and targeted genomic testing may be the most efficient approach. Although subjective clinical improvement was observed in a small number of patients on therapies such as ketogenic diet and dichloroacetate, no evidence-based effective therapy exists. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of human development on safety consciousness in construction.

PubMed

Baradan, Selim; Dikmen, Seyyit Umit; Akboga Kale, Ozge

2018-05-03

The International Labour Organization (ILO) reports that the risk of fatal occupational injuries in developing countries is almost twice as high as in developed countries, indicating a potential relationship between the fatality rates and the development level. The human development index (HDI), based on life expectancy, knowledge level and purchasing power parity, endorsed by the United Nations Development Programme, is a widely accepted measure of the development level. This study investigates the relationship between the HDI and the fatality rates reported by the ILO. A 23-country data set is used to demonstrate the general trend of the relationship followed by country-specific analyses for Australia, Spain, Hungary and Turkey. The study conducted is limited to fatal occupational injuries in construction, where the accidents are notoriously high. The results demonstrate a statistically significant inverse relationship between the fatality rates and the HDI.

Gene Therapy for Diabetes Mellitus in Rats by Hepatic Expression of Insulin

NASA Astrophysics Data System (ADS)

Kolodka, Tadeusz M.; Finegold, Milton; Moss, Larry; Woo, Savio L. C.

1995-04-01

Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic β cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.

Glucose-6-phosphate dehydrogenase deficiency, chlorproguanil-dapsone with artesunate and post-treatment haemolysis in African children treated for uncomplicated malaria.

PubMed

Van Malderen, Carine; Van Geertruyden, Jean-Pierre; Machevo, Sonia; González, Raquel; Bassat, Quique; Talisuna, Ambrose; Yeka, Adoke; Nabasumba, Carolyn; Piola, Patrice; Daniel, Atwine; Turyakira, Eleanor; Forret, Pascale; Van Overmeir, Chantal; van Loen, Harry; Robert, Annie; D' Alessandro, Umberto

2012-07-10

Malaria is a leading cause of mortality, particularly in sub-Saharan African children. Prompt and efficacious treatment is important as patients may progress within a few hours to severe and possibly fatal disease. Chlorproguanil-dapsone-artesunate (CDA) was a promising artemisinin-based combination therapy (ACT), but its development was prematurely stopped because of safety concerns secondary to its associated risk of haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. The objective of the study was to assess whether CDA treatment and G6PD deficiency are risk factors for a post-treatment haemoglobin drop in African children<5 years of age with uncomplicated malaria. This case-control study was performed in the context of a larger multicentre randomized clinical trial comparing safety and efficacy of four different ACT in children with uncomplicated malaria. Children, who after treatment experienced a haemoglobin drop≥2 g/dl (cases) within the first four days (days 0, 1, 2, and 3), were compared with those without an Hb drop (controls). Cases and controls were matched for study site, sex, age and baseline haemoglobin measurements. Data were analysed using a conditional logistic regression model. G6PD deficiency prevalence, homo- or hemizygous, was 8.5% (10/117) in cases and 6.8% (16/234) in controls (p=0.56). The risk of a Hb drop≥2 g/dl was not associated with either G6PD deficiency (adjusted odds ratio (AOR): 0.81; p=0.76) or CDA treatment (AOR: 1.28; p=0.37) alone. However, patients having both risk factors tended to have higher odds (AOR: 11.13; p=0.25) of experiencing a Hb drop≥2 g/dl within the first four days after treatment, however this finding was not statistically significant, mainly because G6PD deficient patients treated with CDA were very few. In non-G6PD deficient individuals, the proportion of cases was similar between treatment groups while in G6PD-deficient individuals, haemolytic anaemia occurred more frequently in children treated with CDA (56%) than in those treated with other ACT (29%), though the difference was not significant (p=0.49). The use of CDA for treating uncomplicated malaria may increase the risk of haemolytic anaemia in G6PD-deficient children.

Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency.

PubMed

Tzvetkov, Mladen V; Matthaei, Johannes; Pojar, Sherin; Faltraco, Frank; Vogler, Sabrina; Prukop, Thomas; Seitz, Tina; Brockmöller, Jürgen

2018-05-01

Fenoterol is a widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter 1 (OCT1), a trait observed in 3% of Europeans and white Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity, and OCT1 inhibition in human hepatocytes reduced fenoterol uptake threefold. After administration of 180 µg of fenoterol to 39 healthy individuals, the OCT1-deficient individuals (zero active OCT1 alleles; n = 5) showed 1.9-fold greater systemic fenoterol exposure (P = 4.0 × 10 -5 ) and 1.7-fold lower volume of distribution (P = 8.0 × 10 -5 ). Correspondingly, the OCT1-deficient individuals had a 1.5-fold stronger increase in heart rate (P = 0.002), a 3.4-fold greater increase in blood glucose (P = 3.0 × 10 -5 ), and significantly lower serum potassium levels. In conclusion, heritable OCT1 deficiency significantly increases plasma concentrations of fenoterol and may be an important factor underlying the excess mortality associated with fenoterol. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Multidisciplinary management of ornithine transcarbamylase (OTC) deficiency in pregnancy: essential to prevent hyperammonemic complications

PubMed Central

Lamb, Stephanie; Aye, Christina Yi Ling; Murphy, Elaine; Mackillop, Lucy

2013-01-01

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error in the metabolism of the urea cycle with an incidence of 1 in 14 000 live births. Pregnancy can trigger potentially fatal hyperammonemic crises. We report a successful pregnancy in a 29-year-old primiparous patient with a known diagnosis of OTC deficiency since infancy. Hyperammonemic complications were avoided due to careful multidisciplinary management which included a detailed antenatal, intrapartum and postnatal plan. Management principles include avoidance of triggers, a low-protein diet and medications which promote the removal of nitrogen by alternative pathways. Triggers include metabolic stress such as febrile illness, particularly gastroenteritis, fasting and any protein loading. In our case the patient, in addition to a restricted protein intake, was prescribed sodium benzoate 4 g four times a day, sodium phenylbutyrate 2 g four times a day and arginine 500 mg four times a day to aid excretion of ammonia and reduce flux through the urea cycle. PMID:23283608

Bioluminescent Imaging Reveals Divergent Viral Pathogenesis in Two Strains of Stat1-Deficient Mice, and in αßγ Interferon Receptor-Deficient Mice

PubMed Central

Pasieka, Tracy Jo; Collins, Lynne; O'Connor, Megan A.; Chen, Yufei; Parker, Zachary M.; Berwin, Brent L.; Piwnica-Worms, David R.; Leib, David A.

2011-01-01

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factor signal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat1−/− and IFNαßγR−/− mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat1−/− mice and in IFNαßγR−/− mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat1−/− (N-term)) had transient infection of the liver and spleen, but succumbed to encephalitis by day 10 post-infection. In stark contrast, infection of IFNαßγR−/− mice was rapidly fatal, with associated viremia and fulminant infection of the liver and spleen, with infected infiltrating cells being primarily of the monocyte/macrophage lineage. To resolve the surprising difference between Stat1−/− and IFNαßγR−/− mice, we infected an additional Stat1−/− strain deleted in the DNA-binding domain (129Stat1−/− (DBD)). These 129Stat1−/− (DBD) mice recapitulated the lethal pattern of liver and spleen infection seen following infection of IFNαßγR−/− mice. This lethal pattern was also observed when 129Stat1−/− (N-term) mice were infected and treated with a Type I IFN-blocking antibody, and immune cells derived from 129Stat1−/− (N-term) mice were shown to be responsive to Type I IFN. These data therefore show significant differences in viral pathogenesis between two commonly-used Stat1−/− mouse strains. The data are consistent with the hypothesis that Stat1−/− (N-term) mice have residual Type I IFN receptor-dependent IFN responses. Complete loss of IFN signaling pathways allows viremia and rapid viral spread with a fatal infection of the liver. This study underscores the importance of careful comparisons between knockout mouse strains in viral pathogenesis, and may also be relevant to the causation of HSV hepatitis in humans, a rare but frequently fatal infection. PMID:21915277

Dystrophic heart failure blocked by membrane sealant poloxamer

NASA Astrophysics Data System (ADS)

Yasuda, Soichiro; Townsend, Dewayne; Michele, Daniel E.; Favre, Elizabeth G.; Day, Sharlene M.; Metzger, Joseph M.

2005-08-01

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD) in humans, an inherited and progressive disease of striated muscle deterioration that frequently involves pronounced cardiomyopathy. Heart failure is the second leading cause of fatalities in DMD. Progress towards defining the molecular basis of disease in DMD has mostly come from studies on skeletal muscle, with comparatively little attention directed to cardiac muscle. The pathophysiological mechanisms involved in cardiac myocytes may differ significantly from skeletal myofibres; this is underscored by the presence of significant cardiac disease in patients with truncated or reduced levels of dystrophin but without skeletal muscle disease. Here we show that intact, isolated dystrophin-deficient cardiac myocytes have reduced compliance and increased susceptibility to stretch-mediated calcium overload, leading to cell contracture and death, and that application of the membrane sealant poloxamer 188 corrects these defects in vitro. In vivo administration of poloxamer 188 to dystrophic mice instantly improved ventricular geometry and blocked the development of acute cardiac failure during a dobutamine-mediated stress protocol. Once issues relating to optimal dosing and long-term effects of poloxamer 188 in humans have been resolved, chemical-based membrane sealants could represent a new therapeutic approach for preventing or reversing the progression of cardiomyopathy and heart failure in muscular dystrophy.

Safe and Efficient Gene Therapy for Pyruvate Kinase Deficiency.

PubMed

Garcia-Gomez, Maria; Calabria, Andrea; Garcia-Bravo, Maria; Benedicenti, Fabrizio; Kosinski, Penelope; López-Manzaneda, Sergio; Hill, Collin; Del Mar Mañu-Pereira, María; Martín, Miguel A; Orman, Israel; Vives-Corrons, Joan-LLuis; Kung, Charles; Schambach, Axel; Jin, Shengfang; Bueren, Juan A; Montini, Eugenio; Navarro, Susana; Segovia, Jose C

2016-08-01

Pyruvate kinase deficiency (PKD) is a monogenic metabolic disease caused by mutations in the PKLR gene that leads to hemolytic anemia of variable symptomatology and that can be fatal during the neonatal period. PKD recessive inheritance trait and its curative treatment by allogeneic bone marrow transplantation provide an ideal scenario for developing gene therapy approaches. Here, we provide a preclinical gene therapy for PKD based on a lentiviral vector harboring the hPGK eukaryotic promoter that drives the expression of the PKLR cDNA. This therapeutic vector was used to transduce mouse PKD hematopoietic stem cells (HSCs) that were subsequently transplanted into myeloablated PKD mice. Ectopic RPK expression normalized the erythroid compartment correcting the hematological phenotype and reverting organ pathology. Metabolomic studies demonstrated functional correction of the glycolytic pathway in RBCs derived from genetically corrected PKD HSCs, with no metabolic disturbances in leukocytes. The analysis of the lentiviral insertion sites in the genome of transplanted hematopoietic cells demonstrated no evidence of genotoxicity in any of the transplanted animals. Overall, our results underscore the therapeutic potential of the hPGK-coRPK lentiviral vector and provide high expectations toward the gene therapy of PKD and other erythroid metabolic genetic disorders.

Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis.

PubMed

Kida, Taiki; Ayabe, Shinya; Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

2016-01-01

Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis.

Development of ergonomics audits for bagging, haul truck and maintenance and repair operations in mining.

PubMed

Dempsey, Patrick G; Pollard, Jonisha; Porter, William L; Mayton, Alan; Heberger, John R; Gallagher, Sean; Reardon, Leanna; Drury, Colin G

2017-12-01

The development and testing of ergonomics and safety audits for small and bulk bag filling, haul truck and maintenance and repair operations in coal preparation and mineral processing plants found at surface mine sites is described. The content for the audits was derived from diverse sources of information on ergonomics and safety deficiencies including: analysis of injury, illness and fatality data and reports; task analysis; empirical laboratory studies of particular tasks; field studies and observations at mine sites; and maintenance records. These diverse sources of information were utilised to establish construct validity of the modular audits that were developed for use by mine safety personnel. User and interrater reliability testing was carried out prior to finalising the audits. The audits can be implemented using downloadable paper versions or with a free mobile NIOSH-developed Android application called ErgoMine. Practitioner Summary: The methodology used to develop ergonomics audits for three types of mining operations is described. Various sources of audit content are compared and contrasted to serve as a guide for developing ergonomics audits for other occupational contexts.

Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease.

PubMed

Bakker, Jaap A; Drent, Marjolein; Bierau, Jörgen

2007-09-01

Mercaptopurine therapy is increasingly important as immunosuppressive therapy in interstitial lung disease. We focus on human mercaptopurine metabolism and the defects in this metabolism causing adverse drug reactions. Defects in mercaptopurine metabolizing enzymes like thiopurine methyltransferase and inosine triphosphate pyrophosphohydrolase lead to severe adverse drug reactions, sometimes with fatal outcome. Other enzymes, still not thoroughly investigated, can give rise to toxic effects or decreased efficacy in mercaptopurine therapy when the activity of these enzymes is altered. Pharmacogenetic screening of potential patients for mercaptopurine therapy is important to avoid adverse drug reactions caused by inherited enzyme deficiencies in these metabolic pathways. Pretreatment screening for deficiencies of mercaptopurine metabolizing enzymes will significantly reduce the number of patients with an adverse drug reaction and concomitantly associated healthcare costs.

Human babesiosis in Ireland: further observations and the medical significance of this infection.

PubMed

Garnham, P C; Donnelly, J; Hoogstraal, H; Kennedy, C C; Walton, G A

1969-12-27

Three splenectomized persons in Yugoslavia, California, and Ireland have been reported to be infected by three different Babesia species; two cases were fatal. In a study of the site where the fatal infection was contracted in Ireland, blood samples from 36 persons who had recently been bitten by ticks were inoculated into two splenectomized calves; no response to Babesia divergens was detected. Field-collected Ixodes ricinus ticks inoculated into another splenectomized calf resulted in fever and recovery of the agent of tick-borne fever (Cytoecetes phagocytophilia). This attempt to determine the presence of latent infection in human beings with intact spleens should be repeated on a larger scale in areas with a demonstrably high incidence of Babesia in ticks and animals. Few places in the world are free of piroplasms; their presence may present a hazard to splenectomized persons or to those whose splenic function is deficient.

Switching operations fatality analysis : findings and recommendations of the SOFA working group

DOT National Transportation Integrated Search

1999-10-01

On February 1998, a Switching Operations Fatality Analysis (SOFA) Working Group (WG) was formed at the request of the Federal Railroad Administration (FRA) to review recent fatal incidents and develop recommendations for reducing fatalities in switch...

A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations

PubMed Central

2013-01-01

The G6PC3 gene encodes the ubiquitously expressed glucose-6-phosphatase enzyme (G-6-Pase β or G-6-Pase 3 or G6PC3). Bi-allelic G6PC3 mutations cause a multi-system autosomal recessive disorder of G6PC3 deficiency (also called severe congenital neutropenia type 4, MIM 612541). To date, at least 57 patients with G6PC3 deficiency have been described in the literature. G6PC3 deficiency is characterized by severe congenital neutropenia, recurrent bacterial infections, intermittent thrombocytopenia in many patients, a prominent superficial venous pattern and a high incidence of congenital cardiac defects and uro-genital anomalies. The phenotypic spectrum of the condition is wide and includes rare manifestations such as maturation arrest of the myeloid lineage, a normocellular bone marrow, myelokathexis, lymphopaenia, thymic hypoplasia, inflammatory bowel disease, primary pulmonary hypertension, endocrine abnormalities, growth retardation, minor facial dysmorphism, skeletal and integument anomalies amongst others. Dursun syndrome is part of this extended spectrum. G6PC3 deficiency can also result in isolated non-syndromic severe neutropenia. G6PC3 mutations in result in reduced enzyme activity, endoplasmic reticulum stress response, increased rates of apoptosis of affected cells and dysfunction of neutrophil activity. In this review we demonstrate that loss of function in missense G6PC3 mutations likely results from decreased enzyme stability. The condition can be diagnosed by sequencing the G6PC3 gene. A number of G6PC3 founder mutations are known in various populations and a possible genotype-phenotype relationship also exists. G6PC3 deficiency should be considered as part of the differential diagnoses in any patient with unexplained congenital neutropenia. Treatment with G-CSF leads to improvement in neutrophil numbers, prevents infections and improves quality of life. Mildly affected patients can be managed with prophylactic antibiotics. Untreated G6PC3 deficiency can be fatal. Echocardiogram, renal and pelvic ultrasound scans should be performed in all cases of suspected or confirmed G6PC3 deficiency. Routine assessment should include biochemical profile, growth profile and monitoring for development of varicose veins or venous ulcers. PMID:23758768

The burden of childhood injuries and evidence based strategies developed using the injury surveillance system in Pasto, Colombia.

PubMed

Espitia-Hardeman, Victoria; Borse, Nagesh N; Dellinger, Ann M; Betancourt, Carmen Elena; Villareal, Alba Nelly; Caicedo, Luz Diana; Portillo, Carlos

2011-02-01

This article characterises the burden of childhood injuries and provides examples of evidence-based injury prevention strategies developed using a citywide injury surveillance system in Pasto, Colombia. Fatal (2003-2007) and non-fatal (2006-2007) childhood injury data were analysed by age, sex, cause, intent, place of occurrence, and disposition. Boys accounted for 71.5% of fatal and 64.9% of non-fatal injuries. The overall fatality rate for all injuries was 170.8 per 100,000 and the non-fatal injury rate was 4,053 per 100,000. Unintentional injuries were the leading causes of fatal injuries for all age groups, except for those 15-19 years whose top four leading causes were violence-related. Among non-fatal injuries, falls was the leading mechanism in the group 0-14 years. Interpersonal violence with a sharp object was the most important cause for boys aged 15-19 years. Home was the most frequent place of occurrence for both fatal and non-fatal injuries for young children 0-4 years old. Home, school and public places became an important place for injuries for boys in the age group 5-15 years. The highest case-fatality rate was for self-inflicted injuries (8.9%). Although some interventions have been implemented in Pasto to reduce injuries, it is necessary to further explore risk factors to better focus prevention strategies and their evaluation. We discuss three evidence-based strategies developed to prevent firework-related injuries during festival, self-inflicted injuries, and road traffic-related injuries, designed and implemented based on the injury surveillance data.

Genetic analysis of fructose-1,6-bisphosphatase (FBPase) deficiency in nine consanguineous Pakistani families.

PubMed

Ijaz, Sadaqat; Zahoor, Muhammad Yasir; Imran, Muhammad; Ramzan, Khushnooda; Bhinder, Munir Ahmad; Shakeel, Hussain; Iqbal, Muhammad; Aslam, Asim; Shehzad, Wasim; Cheema, Huma Arshad; Rehman, Habib

2017-10-26

Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare inherited metabolic disorder characterized by recurrent episodes of hypoglycemia, ketosis and lactic acidosis. FBPase is encoded by FBP1 gene and catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate in the last step of gluconeogenesis. We report here FBP1 mutations in nine consanguineous Pakistani families affected with FBPase deficiency. Nine families having one or two individuals affected with FBPase deficiency were enrolled over a period of 3 years. All FBP1 exonic regions including splicing sites were PCR-amplified and sequenced bidirectionally. Familial cosegregation of mutations with disease was confirmed by direct sequencing and PCR-RFLP analysis. Three different FBP1 mutations were identified. Each of two previously reported mutations (c.472C>T (p.Arg158Trp) and c.841G>A (p.Glu281Lys)) was carried by four different families. The ninth family carried a novel 4-bp deletion (c.609_612delAAAA), which is predicted to result in frameshift (p.Lys204Argfs*72) and loss of FBPase function. The novel variant was not detected in any of 120 chromosomes from normal ethnically matched individuals. FBPase deficiency is often fatal in the infancy and early childhood. Early diagnosis and prompt treatment is therefore crucial to preventing early mortality. We recommend the use of c.472C>T and c.841G>A mutations as first choice genetic markers for molecular diagnosis of FBPase deficiency in Pakistan.

Pathogenesis of NEC: Role of the Innate and Adaptive Immune Response

PubMed Central

Denning, Timothy L.; Bhatia, Amina M.; Kane, Andrea F.; Patel, Ravi M.; Denning, Patricia L.

2017-01-01

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC. PMID:27940091

Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia.

PubMed Central

Lennard, L; Gibson, B E; Nicole, T; Lilleyman, J S

1993-01-01

Two children with acute lymphoblastic leukaemia (ALL) taking daily 6-mercaptopurine as part of a national UK therapeutic trial repeatedly developed profound myelosuppression on 25% of the standard protocol dose. Both were found to have undetectable intracellular activity of thiopurine methyltransferase (TPMT), an enzyme controlling one of the major alternative catabolic pathways of 6-mercaptopurine, and both produced higher concentrations of cytotoxic drug metabolites at 10-25% of the protocol dose than other patients taking 100%. It is supposed that these patients represent the 0.33% of the normal population constitutionally lacking TPMT. It is important to recognise such individuals both to avoid fatal bone marrow failure through inadvertent overdosage, and to be reassured that an adequate drug effect can be achieved at around 10% of the standard dose. PMID:8257179

The clinical heterogeneity of coenzyme Q10 deficiency results from genotypic differences in the Coq9 gene

PubMed Central

Luna-Sánchez, Marta; Díaz-Casado, Elena; Barca, Emanuele; Tejada, Miguel Ángel; Montilla-García, Ángeles; Cobos, Enrique Javier; Escames, Germaine; Acuña-Castroviejo, Dario; Quinzii, Catarina M; López, Luis Carlos

2015-01-01

Primary coenzyme Q10 (CoQ10) deficiency is due to mutations in genes involved in CoQ biosynthesis. The disease has been associated with five major phenotypes, but a genotype–phenotype correlation is unclear. Here, we compare two mouse models with a genetic modification in Coq9 gene (Coq9Q95X and Coq9R239X), and their responses to 2,4-dihydroxybenzoic acid (2,4-diHB). Coq9R239X mice manifest severe widespread CoQ deficiency associated with fatal encephalomyopathy and respond to 2,4-diHB increasing CoQ levels. In contrast, Coq9Q95X mice exhibit mild CoQ deficiency manifesting with reduction in CI+III activity and mitochondrial respiration in skeletal muscle, and late-onset mild mitochondrial myopathy, which does not respond to 2,4-diHB. We show that these differences are due to the levels of COQ biosynthetic proteins, suggesting that the presence of a truncated version of COQ9 protein in Coq9R239X mice destabilizes the CoQ multiprotein complex. Our study points out the importance of the multiprotein complex for CoQ biosynthesis in mammals, which may provide new insights to understand the genotype–phenotype heterogeneity associated with human CoQ deficiency and may have a potential impact on the treatment of this mitochondrial disorder. PMID:25802402

Red Cell Glucose-6-Phosphate Dehydrogenase Deficiency—A Newly Recognized Cause of Neonatal Jaundice and Kernicterus in Canada

PubMed Central

Naiman, J. Lawrence; Kosoy, Martin H.

1964-01-01

Seven male newborns of Chinese, Greek and Italian origin presented with severe hemolytic jaundice due to red cell glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. In five, the hemolysis was precipitated by inhalation of mothball vapours in the home. Kernicterus was evident upon admission in six infants and was fatal in four of these. G-6-PD deficiency should be suspected as a cause of jaundice in all full-term male infants of these ethnic groups. The diagnosis can be confirmed in any hospital by the methemoglobin reduction test. In areas similar to Toronto, Canada, where these high-risk ethnic groups prevail, the following measures are recommended: (1) detection of G-6-PD deficient newborns by screening cord bloods of all infants of these ethnic groups; (2) protection of affected infants from potentially hemolytic agents such as naphthalene, certain vitamin K preparations, and sulfonamides; and (3) observation of serum bilirubin levels to assess the need for exchange transfusion for hyperbilirubinemia. ImagesFig. 1 PMID:14226101

Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency.

PubMed

Péquignot, M O; Dey, R; Zeviani, M; Tiranti, V; Godinot, C; Poyau, A; Sue, C; Di Mauro, S; Abitbol, M; Marsac, C

2001-05-01

Cytochrome c oxidase (COX) deficiency is one of the major causes of Leigh Syndrome (LS), a fatal encephalopathy of infancy or childhood, characterized by symmetrical lesions in the basal ganglia and brainstem. Mutations in the nuclear genes encoding COX subunits have not been found in patients with LS and COX deficiency, but mutations have been identified in SURF1. SURF1 encodes a factor involved in COX biogenesis. To date, 30 different mutations have been reported in 40 unrelated patients. We aim to provide an overview of all known mutations in SURF1, and to propose a common nomenclature. Twelve of the mutations were insertion/deletion mutations in exons 1, 4, 6, 8, and 9; 10 were missense/nonsense mutations in exons 2, 4, 5, 7, and 8; and eight were detected at splicing sites in introns 3 to 7. The most frequent mutation was 312_321del 311_312insAT which was found in 12 patients out of 40. Twenty mutations have been described only once. We also list all polymorphisms discovered to date. Copyright 2001 Wiley-Liss, Inc.

Motor Function and Dopamine Release Measurements in Transgenic Huntington’s Disease Model Rats

PubMed Central

Ortiz, Andrea N.; Osterhaus, Gregory L.; Lauderdale, Kelli; Mahoney, Luke; Fowler, Stephen C.; von Hörsten, Stephan; Riess, Olaf; Johnson, Michael A.

2013-01-01

Huntington’s disease (HD) is a fatal, genetic, neurodegenerative disorder characterized by deficits in motor and cognitive function. Here, we have quantitatively characterized motor deficiencies and dopamine release dynamics in transgenic HD model rats. Behavioral analyses were conducted using a newly-developed force-sensing runway and a previously-developed force-plate actometer. Gait disturbances were readily observed in transgenic HD rats at 12 to 15 months of age. Additionally, dopamine system challenge by ip injection of amphetamine also revealed that these rats were resistant to the expression of focused stereotypy compared to wild-type controls. Moreover, dopamine release, evoked by the application of single and multiple electrical stimulus pulses applied at different frequencies, and measured using fast-scan cyclic voltammetry at carbon-fiber microelectrodes, was diminished in transgenic HD rats compared to age-matched wild-type control rats. Collectively, these results underscore the potential contribution of dopamine release alterations to the expression of motor impairments in transgenic HD rats. PMID:22418060

Analyses of fatalities from natural catastrophes in different income groups over time

NASA Astrophysics Data System (ADS)

Grimm, Tobias

2017-04-01

Identifying not only economic and insured losses but also numbers of fatalities from natural catastrophes provides new information on resilience and prevention measures in the countries affected. In this talk, we examine how fatalities from Munich Re's NatCatSERVICE database, caused by natural disasters have developed. In addition to the standard approach based on fatalities by country, we introduced a new measure, "fatalities per million inhabitants", and factored in population development over time. The World Bank definition was used to determine the wealth classification of individual countries. This methodology enables us to compare countries with different population sizes and thus produce an index for humanitarian impact. The analyses are key information on ascertaining whether prevention measures or early-warning systems have in fact reduced the number of fatalities in recent decades (1980-2016).

HIV-related risk perception among female sex workers in Nigeria

PubMed Central

Ankomah, Augustine; Omoregie, Godpower; Akinyemi, Zacch; Anyanti, Jennifer; Ladipo, Olaronke; Adebayo, Samson

2011-01-01

Background Over one-third of sex workers in Nigeria are infected with human immunodeficiency virus (HIV), yet there is a lack of understanding of sex workers’ own perception of sexual risk-taking. Applying the theory of cognitive dissonance, this paper examined the personal HIV risk perception of brothel-based sex workers. Methods The study is based on 24 focus group discussions held among brothel-based sex workers in four geographically and culturally dispersed cities in Nigeria. Results It was found that sex workers underestimated their risk of infection and rationalized, defended, or justified their behaviors, a typical psychological response to worry, threat, and anxiety arising from the apparent discrepancies between beliefs and behaviors. To reduce dissonance, many sex workers had a strong belief in fatalism, predestination, and faith-based invulnerability to HIV infection. Many believed that one will not die of acquired immune deficiency syndrome if it is not ordained by God. The sex workers also had a high level of HIV-related stigma. Conclusion From these findings, most sex workers considered risk reduction and in particular condom use as far beyond their control or even unnecessary, as a result of their strong beliefs in fatalism and predestination. Therefore, one critical area of intervention is the need to assist sex workers to develop accurate means of assessing their personal vulnerability and self-appraisal of HIV-related risk. PMID:22096411

Role of Gamma Interferon in the Pathogenesis of Severe Schistosomiasis in Interleukin-4-Deficient Mice

PubMed Central

La Flamme, Anne Camille; Patton, Elisabeth A.; Pearce, Edward J.

2001-01-01

In the absence of interleukin-4 (IL-4), infection with Schistosoma mansoni leads to a severe fatal disease rather than the chronic survivable condition that occurs in wild-type (WT) mice. Because the sustained production of NO most closely correlates to weight loss and fatality in infected IL-4−/− mice and because gamma interferon (IFN-γ) is an important inducer of inducible NO synthase, infected IL-4−/− mice were treated with anti-IFN-γ antibodies to determine the role of IFN-γ during schistosomiasis in WT and IL-4−/− animals. When IFN-γ was neutralized, Th2 responses were enhanced and NO production was reduced in both WT and IL-4−/− mice. The decreased NO production correlated with a rescue of proliferation in splenocytes from infected IL-4−/− mice. Furthermore, the neutralization of IFN-γ in vivo improved the gross appearance of the liver and led to a reduction in granuloma size in infected IL-4−/− but not WT mice. However, the neutralization of IFN-γ in vivo did not affect the development of severe disease in infected IL-4−/− mice. These results suggest that while the increased production of IFN-γ does lead to some of the pathology observed in infected IL-4−/− mice, it is not ultimately responsible for cachexia and death. PMID:11705919

Use of fatal real-life crashes to analyze a safe road transport system model, including the road user, the vehicle, and the road.

PubMed

Stigson, Helena; Krafft, Maria; Tingvall, Claes

2008-10-01

To evaluate if the Swedish Road Administration (SRA) model for a safe road transport system, which includes the interaction between the road user, the vehicle, and the road, could be used to classify fatal car crashes according to some safety indicators. Also, to present a development of the model to better identify system weakness. Real-life crashes with a fatal outcome were classified according to the vehicle's safety rating by Euro NCAP (European Road Assessment Programme) and fitment of ESC (Electronic Stability Control). For each crash, the road was also classified according to EuroRAP (European Road Assessment Programme) criteria, and human behavior in terms of speeding, seat belt use, and driving under the influence of alcohol. Each crash was compared with the model criteria, to identify components that might have contributed to fatal outcome. All fatal crashes where a car occupant was killed that occurred in Sweden during 2004 were included: in all, 215 crashes with 248 fatalities. The data were collected from the in-depth fatal crash data of the Swedish Road Administration (SRA). It was possible to classify 93% of the fatal car crashes according to the SRA model. A number of shortcomings in the criteria were identified since the model did not address rear-end or animal collisions or collisions with stationary/parked vehicles or trailers (18 out of 248 cases). Using the further developed model, it was possible to identify that most of the crashes occurred when two or all three components interacted (in 85 of the total 230 cases). Noncompliance with safety criteria for the road user, the vehicle, and the road led to fatal outcome in 43, 27, and 75 cases, respectively. The SRA model was found to be useful for classifying fatal crashes but needs to be further developed to identify how the components interact and thereby identify weaknesses in the road traffic system. This developed model might be a tool to systematically identify which of the components are linked to fatal outcome. In the presented study, fatal outcomes were mostly related to an interaction between the three components: the road, the vehicle, and the road user. Of the three components, the road was the one that was most often linked to a fatal outcome.

Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease.

PubMed

Nitschke, Felix; Sullivan, Mitchell A; Wang, Peixiang; Zhao, Xiaochu; Chown, Erin E; Perri, Ami M; Israelian, Lori; Juana-López, Lucia; Bovolenta, Paola; Rodríguez de Córdoba, Santiago; Steup, Martin; Minassian, Berge A

2017-07-01

Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently challenged by the observation that phosphatase-inactive laforin rescues the laforin-deficient LD mouse model, apparently through correction of a general autophagy impairment. We were for the first time able to quantify brain glycogen phosphate. We also measured glycogen content and chain lengths, LBs, and autophagy markers in several laforin- or malin-deficient mouse lines expressing phosphatase-inactive laforin. We find that: (i) in laforin-deficient mice, phosphatase-inactive laforin corrects glycogen chain lengths, and not hyperphosphorylation, which leads to correction of glycogen amounts and prevention of LBs; (ii) in malin-deficient mice, phosphatase-inactive laforin confers no correction; (iii) general impairment of autophagy is not necessary in LD We conclude that laforin's principle function is to control glycogen chain lengths, in a malin-dependent fashion, and that loss of this control underlies LD. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Sudden Deaths Among Oil and Gas Extraction Workers Resulting from Oxygen Deficiency and Inhalation of Hydrocarbon Gases and Vapors - United States, January 2010-March 2015.

PubMed

Harrison, Robert J; Retzer, Kyla; Kosnett, Michael J; Hodgson, Michael; Jordan, Todd; Ridl, Sophia; Kiefer, Max

2016-01-15

In 2013, an occupational medicine physician from the University of California, San Francisco, contacted CDC's National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA) about two oil and gas extraction worker deaths in the western United States. The suspected cause of these deaths was exposure to hydrocarbon gases and vapors (HGVs) and oxygen (O2)-deficient atmospheres after opening the hatches of hydrocarbon storage tanks. The physician and experts from NIOSH and OSHA reviewed available fatality reports from January 2010 to March 2015, and identified seven additional deaths with similar characteristics (nine total deaths). Recommendations were made to industry and regulators regarding the hazards associated with opening hatches of tanks, and controls to reduce or eliminate the potential for HGV exposure were proposed. Health care professionals who treat or evaluate oil and gas workers need to be aware that workers might report symptoms of exposure to high concentrations of HGVs and possible O2 deficiency; employers and workers need to be aware of this hazard and know how to limit exposure. Medical examiners investigating the death of oil and gas workers who open tank hatches should consider the contribution of O2 deficiency and HGV exposure.

2006 railroad employee fatalities : case studies and analysis

DOT National Transportation Integrated Search

2008-02-01

This document, entitled 2006 Railroad Employee Fatalities: Case Studies and Analysis, was : developed to promote and enhance awareness of many unsafe behaviors and conditions that : typically contribute to railroad employee fatalities, and is i...

The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

PubMed

Levi, Z; Kariv, R; Barnes-Kedar, I; Goldberg, Y; Half, E; Morgentern, S; Eli, B; Baris, H N; Vilkin, A; Belfer, R G; Niv, Y; Elhasid, R; Dvir, R; Abu-Freha, N; Cohen, S

2015-11-01

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acne conglobata in a long-term survivor with trisomy 13, accompanied by selective IgM deficiency.

PubMed

Inoue, Chiyoko N; Tanaka, Yoshiko; Tabata, Nobuko

2017-05-07

Trisomy 13 (T13) is a congenital chromosomal disorder that is usually fatal within 2 years of birth, and only a few patients have been reported to reach adolescence. Here, we report a male long-term survivor of T13, currently 15 years of age, with a several-year history of extensive acne conglobata (AC) with abscesses on the face and neck. Methicillin-resistant Staphylococcus aureus was consistently isolated from the pustular lesions. Serum IgM levels were extremely low at 10 mg/dl. There were no abnormalities in neutrophil and total B cell number, or in serum IgA and IgG levels. Increased CD8+ T cell counts and inversion of the CD4/CD8 ratio were observed repeatedly. The patient's clinical features and laboratory data support a diagnosis of selective IgM deficiency (SIgMD) with concurrent AC. Immunoglobulin replacement therapy elevated serum IgM levels to the normal range and reduced the severity of AC. We suggest that T13 may represent a syndromic disorder associated with multiple organ malformation and a risk of developing immunodeficiency involving SIgMD. Because pediatric SIgMD is rare and an immunological abnormality in T13 patients has not previously been reported, we describe the patient's clinical course. © 2017 Wiley Periodicals, Inc.

A collision risk model to predict avian fatalities at wind facilities: an example using golden eagles, Aquila chrysaetos

USGS Publications Warehouse

New, Leslie; Bjerre, Emily; Millsap, Brian A.; Otto, Mark C.; Runge, Michael C.

2015-01-01

Wind power is a major candidate in the search for clean, renewable energy. Beyond the technical and economic challenges of wind energy development are environmental issues that may restrict its growth. Avian fatalities due to collisions with rotating turbine blades are a leading concern and there is considerable uncertainty surrounding avian collision risk at wind facilities. This uncertainty is not reflected in many models currently used to predict the avian fatalities that would result from proposed wind developments. We introduce a method to predict fatalities at wind facilities, based on pre-construction monitoring. Our method can directly incorporate uncertainty into the estimates of avian fatalities and can be updated if information on the true number of fatalities becomes available from post-construction carcass monitoring. Our model considers only three parameters: hazardous footprint, bird exposure to turbines and collision probability. By using a Bayesian analytical framework we account for uncertainties in these values, which are then reflected in our predictions and can be reduced through subsequent data collection. The simplicity of our approach makes it accessible to ecologists concerned with the impact of wind development, as well as to managers, policy makers and industry interested in its implementation in real-world decision contexts. We demonstrate the utility of our method by predicting golden eagle (Aquila chrysaetos) fatalities at a wind installation in the United States. Using pre-construction data, we predicted 7.48 eagle fatalities year-1 (95% CI: (1.1, 19.81)). The U.S. Fish and Wildlife Service uses the 80th quantile (11.0 eagle fatalities year-1) in their permitting process to ensure there is only a 20% chance a wind facility exceeds the authorized fatalities. Once data were available from two-years of post-construction monitoring, we updated the fatality estimate to 4.8 eagle fatalities year-1 (95% CI: (1.76, 9.4); 80th quantile, 6.3). In this case, the increased precision in the fatality prediction lowered the level of authorized take, and thus lowered the required amount of compensatory mitigation.

A Collision Risk Model to Predict Avian Fatalities at Wind Facilities: An Example Using Golden Eagles, Aquila chrysaetos

PubMed Central

New, Leslie; Bjerre, Emily; Millsap, Brian; Otto, Mark C.; Runge, Michael C.

2015-01-01

Wind power is a major candidate in the search for clean, renewable energy. Beyond the technical and economic challenges of wind energy development are environmental issues that may restrict its growth. Avian fatalities due to collisions with rotating turbine blades are a leading concern and there is considerable uncertainty surrounding avian collision risk at wind facilities. This uncertainty is not reflected in many models currently used to predict the avian fatalities that would result from proposed wind developments. We introduce a method to predict fatalities at wind facilities, based on pre-construction monitoring. Our method can directly incorporate uncertainty into the estimates of avian fatalities and can be updated if information on the true number of fatalities becomes available from post-construction carcass monitoring. Our model considers only three parameters: hazardous footprint, bird exposure to turbines and collision probability. By using a Bayesian analytical framework we account for uncertainties in these values, which are then reflected in our predictions and can be reduced through subsequent data collection. The simplicity of our approach makes it accessible to ecologists concerned with the impact of wind development, as well as to managers, policy makers and industry interested in its implementation in real-world decision contexts. We demonstrate the utility of our method by predicting golden eagle (Aquila chrysaetos) fatalities at a wind installation in the United States. Using pre-construction data, we predicted 7.48 eagle fatalities year-1 (95% CI: (1.1, 19.81)). The U.S. Fish and Wildlife Service uses the 80th quantile (11.0 eagle fatalities year-1) in their permitting process to ensure there is only a 20% chance a wind facility exceeds the authorized fatalities. Once data were available from two-years of post-construction monitoring, we updated the fatality estimate to 4.8 eagle fatalities year-1 (95% CI: (1.76, 9.4); 80th quantile, 6.3). In this case, the increased precision in the fatality prediction lowered the level of authorized take, and thus lowered the required amount of compensatory mitigation. PMID:26134412

A Collision Risk Model to Predict Avian Fatalities at Wind Facilities: An Example Using Golden Eagles, Aquila chrysaetos.

PubMed

New, Leslie; Bjerre, Emily; Millsap, Brian; Otto, Mark C; Runge, Michael C

2015-01-01

Wind power is a major candidate in the search for clean, renewable energy. Beyond the technical and economic challenges of wind energy development are environmental issues that may restrict its growth. Avian fatalities due to collisions with rotating turbine blades are a leading concern and there is considerable uncertainty surrounding avian collision risk at wind facilities. This uncertainty is not reflected in many models currently used to predict the avian fatalities that would result from proposed wind developments. We introduce a method to predict fatalities at wind facilities, based on pre-construction monitoring. Our method can directly incorporate uncertainty into the estimates of avian fatalities and can be updated if information on the true number of fatalities becomes available from post-construction carcass monitoring. Our model considers only three parameters: hazardous footprint, bird exposure to turbines and collision probability. By using a Bayesian analytical framework we account for uncertainties in these values, which are then reflected in our predictions and can be reduced through subsequent data collection. The simplicity of our approach makes it accessible to ecologists concerned with the impact of wind development, as well as to managers, policy makers and industry interested in its implementation in real-world decision contexts. We demonstrate the utility of our method by predicting golden eagle (Aquila chrysaetos) fatalities at a wind installation in the United States. Using pre-construction data, we predicted 7.48 eagle fatalities year-1 (95% CI: (1.1, 19.81)). The U.S. Fish and Wildlife Service uses the 80th quantile (11.0 eagle fatalities year-1) in their permitting process to ensure there is only a 20% chance a wind facility exceeds the authorized fatalities. Once data were available from two-years of post-construction monitoring, we updated the fatality estimate to 4.8 eagle fatalities year-1 (95% CI: (1.76, 9.4); 80th quantile, 6.3). In this case, the increased precision in the fatality prediction lowered the level of authorized take, and thus lowered the required amount of compensatory mitigation.

Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.

PubMed

Ojha, Rohit P; Stallings-Smith, Sericea; Aviles-Robles, Martha J; Gomez, Sergio; Somarriba, María Mercedes; Caniza, Miguela A

2016-04-01

Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from pediatric cancer patients in developed countries may be generalizable to pediatric cancer patients in developing countries.

Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

PubMed

Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

2013-01-01

Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/-) mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/-) mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/-) mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect β-Oxidation

PubMed Central

von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

2013-01-01

Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2−/−) that progressively loses its mtDNA. The TK2−/− mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2−/− mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2−/− mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2−/− mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2−/− mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies. PMID:23505564

Minimizing preventable trauma deaths in a limited-resource setting: a test-case of a multidisciplinary panel review approach at the Komfo Anokye Teaching Hospital in Ghana.

PubMed

Yeboah, Dominic; Mock, Charles; Karikari, Patrick; Agyei-Baffour, Peter; Donkor, Peter; Ebel, Beth

2014-07-01

Our objectives were to determine the proportion of preventable trauma deaths at a large trauma hospital in Kumasi, Ghana, and to identify opportunities for the improvement of trauma care. A multidisciplinary panel of experts evaluated pre-hospital, hospital, and postmortem data of consecutive trauma patients who died over a 5-month period in 2006-2007 at the Komfo Anokye Teaching Hospital. The panel judged the preventability of each death. For preventable and potentially preventable deaths, deficiencies in care that contributed to their deaths were identified. The panel reviewed 231 trauma deaths. Of these, 84 charts had sufficient information to review preventable factors. The panel determined that 23 % of trauma deaths were definitely preventable, 37 % were potentially preventable, and 40 % were not preventable. One main deficiency in care was identified for each of the 50 definitely preventable and potentially preventable deaths. The most common deficiencies were pre-hospital delays (44 % of the 50 deficiencies), delay in treatment (32 %), and inadequate fluid resuscitation (22 %). Among the 19 definitely preventable deaths, the most common cause of death was hemorrhage (47 %), and the most common deficiencies were inadequate fluid resuscitation (37 % of deficiencies in this group) and pre-hospital delay (37 %). A high proportion of trauma fatalities might have been preventable by decreasing pre-hospital delays, adequate resuscitation in hospital, and earlier initiation of care, including definitive surgical management. The study also showed that preventable death panel reviews are a feasible and useful quality improvement method in the study setting.

Development of multivariate exposure and fatal accident involvement rates for 1977

DOT National Transportation Integrated Search

1985-10-01

The need for multivariate accident involvement rates is often encounted in : accident analysis. The FARS (Fatal Accident Reporting System) files contain : records of fatal involvements characterized by many variables while NPTS : (National Personal T...

Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development.

PubMed

Molloy, Anne M; Kirke, Peadar N; Brody, Lawrence C; Scott, John M; Mills, James L

2008-06-01

The importance of folate in reproduction can be appreciated by considering that the existence of the vitamin was first suspected from efforts to explain a potentially fatal megaloblastic anemia in young pregnant women in India. Today, low maternal folate status during pregnancy and lactation remains a significant cause of maternal morbidity in some communities. The folate status of the neonate tends to be protected at the expense of maternal stores; nevertheless, there is mounting evidence that inadequate maternal folate status during pregnancy may lead to low infant birthweight, thereby conferring risk of developmental and long-term adverse health outcomes. Moreover, folate-related anemia during childhood and adolescence might predispose children to further infections and disease. The role of folic acid in prevention of neural tube defects (NTD) is now established, and several studies suggest that this protection may extend to some other birth defects. In terms of maternal health, clinical vitamin B12 deficiency may be a cause of infertility or recurrent spontaneous abortion. Starting pregnancy with an inadequate vitamin B12 status may increase risk of birth defects such as NTD, and may contribute to preterm delivery, although this needs further evaluation. Furthermore, inadequate vitamin B12 status in the mother may lead to frank deficiency in the infant if sufficient fetal stores of vitamin B12 are not laid down during pregnancy or are not available in breastmilk. However, the implications of starting pregnancy and lactation with low vitamin B12 status have not been sufficiently researched.

Dapsone-induced agranulocytosis-possible involvement of low-activity N-acetyltransferase 2.

PubMed

Potočnjak, Ines; Likić, Robert; Šimić, Iveta; Juričić Nahal, Danica; Čegec, Ivana; Ganoci, Lana; Božina, Nada

2017-10-01

Dapsone-induced agranulocytosis is a rare but potentially fatal adverse drug reaction (ADR). A 45-year-old male Caucasian patient developed agranulocytosis caused by dapsone (diamino-diphenyl sulfone), which he was prescribed for leukocytoclastic vasculitis. Patient's treatment consisted of termination of dapsone, antibiotic therapy, and granulocyte colony-stimulating factor leading to prompt improvement of symptoms and normalization of laboratory blood values. Diagnostic evaluation revealed methemoglobinemia and excluded glucose-6-phosphate dehydrogenase deficiency. Pharmacogenetics testing showed that he was a carrier of NAT2 *5/*6 genotype, predisposing to low activity of the N-acetyltransferase 2 enzyme. This was the first and only ADR to dapsone reported in Croatia. In total, there have been 73 ADR to dapsone recorded worldwide, including only four cases of agranulocytosis. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration

PubMed Central

Hoover, Brian R.; Reed, Miranda N.; Su, Jianjun; Penrod, Rachel D.; Kotilinek, Linda A.; Grant, Marianne K.; Pitstick, Rose; Carlson, George A.; Lanier, Lorene M.; Yuan, Li-Lian; Ashe, Karen H.; Liao, Dezhi

2010-01-01

The microtubule-associated protein tau accumulates in Alzheimer’s and other fatal dementias, which manifest when forebrain neurons die. Recent advances in understanding these disorders indicate that brain dysfunction precedes neurodegeneration, but the role of tau is unclear. Here, we show that early tau-related deficits develop not from the loss of synapses or neurons, but rather as a result of synaptic abnormalities caused by the accumulation of hyperphosphorylated tau within intact dendritic spines, where it disrupts synaptic function by impairing glutamate receptor trafficking or synaptic anchoring. Mutagenesis of 14 disease-associated serine and threonine amino acid residues to create pseudohyperphosphorylated tau caused tau mislocalization while creation of phosphorylation-deficient tau blocked the mis-targeting of tau to dendritic spines. Thus, tau phosphorylation plays a critical role in mediating tau mislocalization and subsequent synaptic impairment. These data establish that the locus of early synaptic malfunction caused by tau resides in dendritic spines. PMID:21172610

Extended investigation on road fatality in Brunei.

PubMed

Yusof, N B; Hoque, M A; Steele, M C; Yong, S Y

2018-06-08

Road fatality is one of the leading causes of death in Brunei with 79 deaths in 1993, the highest ever recorded. The Brunei government has been trying to reduce this by implementing new traffic measures and successfully reduced fatalities to 24 fatalities in 2014. Yearly road fatality has been fluctuating, but there has been a declining tendency overall. The aim of this study is to investigate road fatality in Brunei by extending the research. We developed a multiple regression model and carried out an analysis on road fatality in Brunei. Our analysis indicates that the road fatality appears to rise depending on the increase in the number of young drivers between 15 to 24 years and the number of unemployed people. Comparisons of Brunei road fatality rate per 10,000 vehicles are made with some other countries and we conclude that Brunei has approximately the same rate as Australia in 2014.

Human babesiosis in ireland: Further observations and the medical significance of this infection

PubMed Central

Garnham, P. C. C.; Donnelly, Joseph; Hoogstraal, Harry; Kennedy, C. Cotton; Walton, Gerald A.

1969-01-01

Three splenectomized persons in Yugoslavia, California, and Ireland have been reported to be infected by three different Babesia species; two cases were fatal. In a study of the site where the fatal infection was contracted in Ireland, blood samples from 36 persons who had recently been bitten by ticks were inoculated into two splenectomized calves; no response to Babesia divergens was detected. Field-collected Ixodes ricinus ticks inoculated into another splenectomized calf resulted in fever and recovery of the agent of tick-borne fever (Cytoecetes phagocytophilia). This attempt to determine the presence of latent infection in human beings with intact spleens should be repeated on a larger scale in areas with a demonstrably high incidence of Babesia in ticks and animals. Few places in the world are free of piroplasms; their presence may present a hazard to splenectomized persons or to those whose splenic function is deficient. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 1Fig. 2Fig. 3 PMID:4902496

The incidence of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1974-02-01

Methods for the collection of blood, urine, bile and alcohol washes of face and fingers from fatally injured drivers have been developed. Specimens were supplied by coroners and medical examiners from fatally injured drivers. Seven hundred and ten we...

[Results of acyclovir treatment of chickenpox and herpes zoster in children with immune tolerance].

PubMed

Jankowska, H; Szczepańska-Putz, M; Wojnarowski, M

Acyclovir was used for the treatment of Varicella-zoster virus infections in 53 children (10 neonates and 43 children aged between 2 an 15 years) with immunological system deficiency hospitalized at the Department of the Infectious Diseases of Childhood in the Medical Academy in Warszawa. The obtained results of therapy were favourable except one fatal case of the child with visceral dissemination of the virus prior to acyclovir treatment. Compared with other antiviral agents used by the authors previously, acyclovir proved to be the most effective.

Brain gamma-aminobutyric acid deficiency in dialysis encephalopathy.

PubMed

Sweeney, V P; Perry, T L; Price, J D; Reeve, C E; Godolphin, W J; Kish, S J

1985-02-01

We measured levels of gamma-aminobutyric acid (GABA) in the CSF and in the autopsied brain of patients with dialysis encephalopathy. GABA concentrations were low in the CSF of three of five living patients. Mean GABA content was reduced by 30 to 50% in five brain regions (frontal, occipital, and cerebellar cortex, caudate nucleus, and medial dorsal thalamus) in five fatal cases. GABA content was normal in brain regions where GABA is characteristically reduced in Huntington's disease. Choline acetyltransferase activity was diminished (by 25 to 35%) in cerebral cortex of the dialysis encephalopathy patients.

Fatalism and health promoting behaviors in Chinese and Korean immigrants and Caucasians.

PubMed

Heiniger, Louise E; Sherman, Kerry A; Shaw, Laura-Kate E; Costa, Daniel

2015-02-01

Fatalism has been associated with non-adherence to health behavior in the past. This study compared fatalism of Chinese and Korean immigrants with native-born Caucasians (N = 309) and examined whether the relationship between fatalism and exercise, nutrition and medical screening would be moderated by ethnicity. Chinese reported higher fatalism than Caucasians and Koreans. Higher fatalism was associated with greater exercise among Chinese and Koreans, but less reported exercise among Caucasians. Caucasian participants had higher scores for nutrition and medical screening compared with Chinese and Korean immigrants. These findings indicate that fatalism is more prevalent among Chinese immigrants; however, there is no evidence of a detrimental effect of fatalism on exercise, nutrition or medical screening among the Asian immigrants. Caucasians with higher fatalism may be at greater risk of future illnesses, given the association between fatalism and sedentary behavior in this group. Differences between cultural groups in the adoption of health behavior justify the development and assessment of targeted interventions to optimize health promoting behaviors.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

PubMed

Dorgalaleh, Akbar; Alavi, Sayed Ezatolla Rafiee; Tabibian, Shadi; Soori, Shahrzad; Moradi, Es'hagh; Bamedi, Taregh; Asadi, Mansour; Jalalvand, Masumeh; Shamsizadeh, Morteza

2017-05-01

Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. For this study, all relevant publications were searched in Medlin until 2015. Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

PubMed

Hoshi, Yutaka; Okabe, Kohki; Shibasaki, Koji; Funatsu, Takashi; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta

2018-06-20

Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia. SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the thermosensitive cation channel TRPV4 (transient receptor potential vanilloid 4) are involved in the pathology of edema. Finally, we confirmed that TRPV4 is involved in brain edema in vivo using TRPV4-deficient mice, concluding that hyperthermia activates TRPV4 and induces brain edema after ischemia. Copyright © 2018 the authors 0270-6474/18/385700-10$15.00/0.

Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires' Disease - North America, 2000-2014.

PubMed

Garrison, Laurel E; Kunz, Jasen M; Cooley, Laura A; Moore, Matthew R; Lucas, Claressa; Schrag, Stephanie; Sarisky, John; Whitney, Cynthia G

2016-06-10

The number of reported cases of Legionnaires' disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000-2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100,000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires' disease to identify gaps in building water system maintenance and guide prevention efforts. Information from summaries of CDC Legionnaires' disease outbreak investigations during 2000-2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. During 2000-2014, CDC participated in 38 field investigations of Legionnaires' disease. Among 27 land-based outbreaks, the median number of cases was 10 (range = 3-82) and median outbreak case fatality rate was 7% (range = 0%-80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in ≥2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires' disease outbreaks and reducing disease.

Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion.

PubMed

Sun, Ren; Wang, Liya

2014-10-07

Mitochondrial thymidine kinase 2 (TK2) is a nuclear gene-encoded protein, synthesized in the cytosol and subsequently translocated into the mitochondrial matrix, where it catalyzes the phosphorylation of thymidine (dT) and deoxycytidine (dC). The kinetics of dT phosphorylation exhibits negative cooperativity, but dC phosphorylation follows hyperbolic Michaelis-Menten kinetics. The two substrates compete with each other in that dT is a competitive inhibitor of dC phosphorylation, while dC acts as a noncompetitive inhibitor of dT phosphorylation. In addition, TK2 is feedback inhibited by dTTP and dCTP. TK2 also phosphorylates a number of pyrimidine nucleoside analogues used in antiviral and anticancer therapy and thus plays an important role in mitochondrial toxicities caused by nucleoside analogues. Deficiency in TK2 activity due to genetic alterations causes devastating mitochondrial diseases, which are characterized by mitochondrial DNA (mtDNA) depletion or multiple deletions in the affected tissues. Severe TK2 deficiency is associated with early-onset fatal mitochondrial DNA depletion syndrome, while less severe deficiencies result in late-onset phenotypes. In this review, studies of the enzyme kinetic behavior of TK2 enzyme variants are used to explain the mechanism of mtDNA depletion caused by TK2 mutations, thymidine overload due to thymidine phosphorylase deficiency, and mitochondrial toxicity caused by antiviral thymidine analogues.

Analysis of leukotrienes in cerebrospinal fluid of a reference population and patients with inborn errors of metabolism: further evidence for a pathognomonic profile in LTC(4)-synthesis deficiency.

PubMed

Mayatepek, E; Zelezny, R; Hoffmann, G F

2000-02-25

Cysteinyl leukotrienes (LTC(4), LTD(4), LTE(4)) are potent lipid mediators derived from arachidonate in the 5-lipoxygenase pathway. Recently, the first inborn error of leukotriene synthesis, LTC(4)-synthesis deficiency, has been identified in association with a fatal developmental syndrome. The absence of leukotrienes in cerebrospinal fluid was one of the most striking biochemical findings in this disorder. We analysed leukotrienes in cerebrospinal fluid of patients with a broad spectrum of other well-defined inborn errors of metabolism, including glutathione synthetase deficiency (n=2), Zellweger syndrome (n=3), mitochondrial disorders (n=8), fatty acid oxidation defects (n=7), organic acidurias (n=7), neurotransmitter defects (n=5) and patients with non-specific neurological symptoms, as a reference population (n=120). The concentrations of leukotrienes were not related to age. Representative percentiles were calculated as reference intervals of each leukotriene. In all patients with an inborn error of metabolism concentration of cysteinyl leukotrienes and LTB(4) did not differ from the reference group. Our results indicate that absence of cysteinyl leukotrienes (<5 pg/ml) in association with normal or increased LTB(4) (50.0-67.3 pg/ml) is pathognomonic for LTC(4)-synthesis deficiency. The unique profile of leukotrienes in cerebrospinal fluid in this new disorder is primarily related to the defect and represents a new diagnostic approach.

Hereditary alpha-1-antitrypsin deficiency and its clinical consequences.

PubMed

Fregonese, Laura; Stolk, Jan

2008-06-19

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. The end-stage liver and lung disease can be treated by organ transplantation. In AATD patients with cirrhosis, prognosis is generally grave.

Traumatic work related fatalities in commercial fishermen in Australia.

PubMed

Driscoll, T R; Ansari, G; Harrison, J E; Frommer, M S; Ruck, E A

1994-09-01

To describe the types and circumstances of traumatic work related fatalities in Australian commercial fishermen. Work related traumatic fishing fatalities were studied as part of a larger study of all work related traumatic fatalities in Australia from 1982 to 1984. Data on 47 cases were obtained from inspection of coroners' files. The incidence of fatality of 143/100,000 person-years was 18 times higher than the incidence of fatality for the entire workforce, and considerably higher than that of the mining and agricultural workforces. 68% of decedents drowned and 13% died from physical trauma. Rough weather, non-seaworthy vessels, inadequate use of personal flotation devices, and inexperience were associated with many of the fatal incidents. Improved vessel and equipment maintenance, better training of workers, greater use of personal flotation devices, and development of improved clothing and personal flotation devices are recommended.

Molecular insight into mitochondrial DNA depletion syndrome in two patients with novel mutations in the deoxyguanosine kinase and thymidine kinase 2 genes.

PubMed

Wang, Liya; Limongelli, Anna; Vila, Maya R; Carrara, Franco; Zeviani, Massimo; Eriksson, Staffan

2005-01-01

Thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) are the two key enzymes in mitochondrial DNA (mtDNA) precursor synthesis. Deficiencies in TK2 or dGK activity, due to genetic alteration, have been shown to cause tissue-specific depletion of mtDNA. In the case of TK2 deficiency, affected individuals suffer severe myopathy and, in the case of dGK deficiency, devastating liver or multi-systemic disease. Here, we report clinical and biochemical findings from two patients with mtDNA depletion syndrome. Patient A was a compound heterozygote carrying the previously reported T77M mutation and a novel mutation (R161K) in the TK2 gene. Patient B carried a novel mutation (L250S) in the dGK gene. The clinical symptoms of patient A included muscular weakness and exercise intolerance due to a severe mitochondrial myopathy associated with a 92% reduction in mtDNA. There was minimal involvement of other organs. Patient B suffered from rapidly progressive, early onset fatal liver failure associated with profoundly decreased mtDNA levels in liver and, to a lesser extent, in skeletal muscle. Site-directed mutagenesis was used to introduce the mutations detected in patients A and B into the TK2 and dGK cDNAs, respectively. We then characterized each of these recombinant enzymes. Catalytic activities of the three mutant enzymes were reduced to about 2-4% for TK2 and 0.5% for dGK as compared to the wild-type enzymes. Altered competition between dCyd and dThd was observed for the T77M mutant. The residual activities of the two mitochondrial enzymes correlated directly with disease development.

Effects of hematopoietic stem cell transplantation on acyl-CoA oxidase deficiency: a sibling comparison study

PubMed Central

Monuki, Edwin S.; Powers, James; Schwartz, Phillip H.; Watkins, Paul A.; Shi, Yang; Moser, Ann; Shrier, David A.; Waterham, Hans R.; Nugent, Diane J.; Abdenur, Jose E.

2015-01-01

Objective Acyl-CoA oxidase (ACOX1) deficiency is a rare disorder of peroxisomal very-long chain fatty acid oxidation. No reports detailing attempted treatment, longitudinal imaging, or neuropathology exist. We describe the natural history of clinical symptoms and brain imaging in two siblings with ACOX1 deficiency, including the younger sibling's response to allogeneic unrelated donor hematopoietic stem cell transplantation (HSCT). Methods We conducted retrospective chart review to obtain clinical history, neuro-imaging, and neuropathology data. ACOX1 genotyping were performed to confirm the disease. In vitro fibroblast and neural stem cell fatty acid oxidation assays were also performed. Results Both patients experienced a fatal neurodegenerative course, with late-stage cerebellar and cerebral gray matter atrophy. Serial brain magnetic resonance imaging in the younger sibling indicated demyelination began in the medulla and progressed rostrally to include the white matter of the cerebellum, pons, midbrain, and eventually subcortical white matter. The successfully engrafted younger sibling had less brain inflammation, cortical atrophy, and neuronal loss on neuroimaging and neuropathology compared to the untreated older sister. Fibroblasts and stem cells demonstrated deficient very long chain fatty acid oxidation. Interpretation Although HSCT did not halt the course of ACOX1 deficiency, it reduced the extent of white matter inflammation in the brain. Demyelination continued because of ongoing neuronal loss, which may be due to inability of transplant to prevent progression of gray matter disease, adverse effects of chronic corticosteroid use to control graft-versus-host disease, or intervention occurring beyond a critical point for therapeutic efficacy. PMID:24619150

Central Nervous System Pathology Progresses Independently of KC and CXCR2 in Globoid-Cell Leukodystrophy

PubMed Central

Reddy, Adarsh S.; Patel, Jigisha R.; Vogler, Carole; Klein, Robyn S.; Sands, Mark S.

2013-01-01

Globoid-cell Leukodystrophy (GLD; Krabbe’s disease) is a rapidly progressing inherited demyelinating disease caused by a deficiency of the lysosomal enzyme Galactosylceramidase (GALC). Deficiency of GALC leads to altered catabolism of galactosylceramide and the cytotoxic lipid, galactosylsphingosine (psychosine). This leads to a rapidly progressive fatal disease with spasticity, cognitive disability and seizures. The murine model of GLD (Twitcher; GALC−/−) lacks the same enzyme and has similar clinical features. The deficiency of GALC leads to oligodendrocyte death, profound neuroinflammation, and the influx of activated macrophages into the CNS. We showed previously that keratinocyte chemoattractant factor (KC) is highly elevated in the CNS of untreated Twitcher mice and significantly decreases after receiving a relatively effective therapy (bone marrow transplantation combined with gene therapy). The action of KC is mediated through the CXCR2 receptor and is a potent chemoattractant for macrophages and microglia. KC is also involved in oligodendrocyte migration and proliferation. Based on the commonalities between the disease presentation and the functions of KC, we hypothesized that KC and/or CXCR2 contribute to the pathogenesis of GLD. Interestingly, the course of the disease is not significantly altered in KC- or CXCR2-deficient Twitcher mice. There is also no alteration in inflammation or demyelination patterns in these mice. Furthermore, transplantation of CXCR2-deficient bone marrow does not alter the progression of the disease as it does in other models of demyelination. This study highlights the role of multiple redundant cytokines and growth factors in the pathogenesis of GLD. PMID:23755134

ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.

PubMed

Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

2014-11-01

Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this diagnosis was excluded by HIBCH sequencing and normal enzyme activity. In contrast to HIBCH deficiency, the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short-chain enoyl-CoA hydratase (ECHS1 gene). This mitochondrial enzyme is active in several metabolic pathways involving fatty acids and amino acids, including valine, and is immediately upstream of HIBCH in the valine pathway. Both children were compound heterozygous for a c.473C > A (p.A158D) missense mutation and a c.414+3G>C splicing mutation in ECHS1. ECHS1 activity was markedly decreased in cultured fibroblasts from both siblings, ECHS1 protein was undetectable by immunoblot analysis and transfection of patient cells with wild-type ECHS1 rescued ECHS1 activity. The highly reactive metabolites methacrylyl-CoA and acryloyl-CoA accumulate in deficiencies of both ECHS1 and HIBCH and are probably responsible for the brain pathology in both disorders. Deficiency of ECHS1 or HIBCH should be considered in children with Leigh disease. Urine metabolite testing can detect and distinguish between these two disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of urban sprawl and vehicle miles traveled on traffic fatalities.

PubMed

Yeo, Jiho; Park, Sungjin; Jang, Kitae

2015-01-01

Previous research suggests that urban sprawl increases auto-dependency and that excessive auto use increases the risk of traffic fatalities. This indirect effect of urban sprawl on traffic fatalities is compared to non-vehicle miles traveled (VMT)-related direct effect of sprawl on fatalities. We conducted a path analysis to examine the causal linkages among urban sprawl, VMT, traffic fatalities, income, and fuel cost. The path diagram includes 2 major linkages: the direct relationship between urban sprawl and traffic fatalities and the indirect effect on fatalities through increased VMT in sprawling urban areas. To measure the relative strength of these causal linkages, path coefficients are estimated using data collected nationally from 147 urbanized areas in the United States. Through both direct and indirect paths, urban sprawl is associated with greater numbers of traffic fatalities, but the direct effect of sprawl on fatalities is more influential than the indirect effect. Enhancing traffic safety can be achieved by impeding urban sprawl and encouraging compact development. On the other hand, policy tools reducing VMT may be less effective than anticipated for traffic safety.

Neural stem cells for disease modeling of Wolman disease and evaluation of therapeutics.

PubMed

Aguisanda, Francis; Yeh, Charles D; Chen, Catherine Z; Li, Rong; Beers, Jeanette; Zou, Jizhong; Thorne, Natasha; Zheng, Wei

2017-06-28

Wolman disease (WD) is a rare lysosomal storage disorder that is caused by mutations in the LIPA gene encoding lysosomal acid lipase (LAL). Deficiency in LAL function causes accumulation of cholesteryl esters and triglycerides in lysosomes. Fatality usually occurs within the first year of life. While an enzyme replacement therapy has recently become available, there is currently no small-molecule drug treatment for WD. We have generated induced pluripotent stem cells (iPSCs) from two WD patient dermal fibroblast lines and subsequently differentiated them into neural stem cells (NSCs). The WD NSCs exhibited the hallmark disease phenotypes of neutral lipid accumulation, severely deficient LAL activity, and increased LysoTracker dye staining. Enzyme replacement treatment dramatically reduced the WD phenotype in these cells. In addition, δ-tocopherol (DT) and hydroxypropyl-beta-cyclodextrin (HPBCD) significantly reduced lysosomal size in WD NSCs, and an enhanced effect was observed in DT/HPBCD combination therapy. The results demonstrate that these WD NSCs are valid cell-based disease models with characteristic disease phenotypes that can be used to evaluate drug efficacy and screen compounds. DT and HPBCD both reduce LysoTracker dye staining in WD cells. The cells may be used to further dissect the pathology of WD, evaluate compound efficacy, and serve as a platform for high-throughput drug screening to identify new compounds for therapeutic development.

Critical role of CXCL4 in the lung pathogenesis of influenza (H1N1) respiratory infection.

PubMed

Guo, L; Feng, K; Wang, Y C; Mei, J J; Ning, R T; Zheng, H W; Wang, J J; Worthen, G S; Wang, X; Song, J; Li, Q H; Liu, L D

2017-11-01

Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory role in inflammatory diseases. Here we show that CXCL4 is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. Additionally, CXCL4 deficiency decreased leukocyte accumulation in the infected lung with markedly decreased neutrophil infiltration into the lung during early infection and extensive leukocyte, especially lymphocyte accumulation at the late infection stage. Loss of CXCL4 did not affect the activation of adaptive immune T and B lymphocytes during the late stage of lung infection. Further study revealed that CXCL4 deficiency inhibited neutrophil recruitment to the infected mouse lung. Thus the above results identify CXCL4 as a vital immunoregulatory chemokine essential for protecting mice against influenza A virus infection, especially as it affects the development of lung injury and neutrophil mobilization to the inflamed lung.

Deficiency of base excision repair enzyme NEIL3 drives increased predisposition to autoimmunity

PubMed Central

Massaad, Michel J.; Zhou, Jia; Tsuchimoto, Daisuke; Chou, Janet; Jabara, Haifa; Janssen, Erin; Glauzy, Salomé; Olson, Brennan G.; Morbach, Henner; Ohsumi, Toshiro K.; Schmitz, Klaus; Kane, Jennifer; Torisu, Kumiko; Chouery, Eliane; Megarbane, Andre; Kang, Peter B.; Al-Idrissi, Eman; Aldhekri, Hasan; Meffre, Eric; Mizui, Masayuki; Manis, John P.; Al-Herz, Waleed; Wallace, Susan S.; Geha, Raif S.

2016-01-01

Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals. The same homozygous NEIL3 mutation was also identified in an asymptomatic individual who exhibited elevated levels of serum autoantibodies and defective peripheral B cell tolerance, but normal B cell function. Further analysis of the patients revealed an absence of LPS-responsive beige-like anchor (LRBA) protein expression, a known cause of immunodeficiency. We next examined the contribution of NEIL3 to the maintenance of self-tolerance in Neil3–/– mice. Although Neil3–/– mice displayed normal B cell function, they exhibited elevated serum levels of autoantibodies and developed nephritis following treatment with poly(I:C) to mimic microbial stimulation. In Neil3–/– mice, splenic T and B cells as well as germinal center B cells from Peyer’s patches showed marked increases in apoptosis and cell death, indicating the potential release of self-antigens that favor autoimmunity. These findings demonstrate that deficiency in NEIL3 is associated with increased lymphocyte apoptosis, autoantibodies, and predisposition to autoimmunity. PMID:27760045

Hazards of Extreme Weather: Flood Fatalities in Texas

NASA Astrophysics Data System (ADS)

Sharif, H. O.; Jackson, T.; Bin-Shafique, S.

2009-12-01

The Federal Emergency Management Agency (FEMA) considers flooding “America’s Number One Natural Hazard”. Despite flood management efforts in many communities, U.S. flood damages remain high, due, in large part, to increasing population and property development in flood-prone areas. Floods are the leading cause of fatalities related to natural disasters in Texas. Texas leads the nation in flash flood fatalities. There are three times more fatalities in Texas (840) than the following state Pennsylvania (265). This study examined flood fatalities that occurred in Texas between 1960 and 2008. Flood fatality statistics were extracted from three sources: flood fatality databases from the National Climatic Data Center, the Spatial Hazard Event and Loss Database for the United States, and the Texas Department of State Health Services. The data collected for flood fatalities include the date, time, gender, age, location, and weather conditions. Inconsistencies among the three databases were identified and discussed. Analysis reveals that most fatalities result from driving into flood water (about 65%). Spatial analysis indicates that more fatalities occurred in counties containing major urban centers. Hydrologic analysis of a flood event that resulted in five fatalities was performed. A hydrologic model was able to simulate the water level at a location where a vehicle was swept away by flood water resulting in the death of the driver.

Autonomous requirements of the Menkes disease protein in the nervous system.

PubMed

Hodgkinson, Victoria L; Zhu, Sha; Wang, Yanfang; Ladomersky, Erik; Nickelson, Karen; Weisman, Gary A; Lee, Jaekwon; Gitlin, Jonathan D; Petris, Michael J

2015-11-15

Menkes disease is a fatal neurodegenerative disorder arising from a systemic copper deficiency caused by loss-of-function mutations in a ubiquitously expressed copper transporter, ATP7A. Although this disorder reveals an essential role for copper in the developing human nervous system, the role of ATP7A in the pathogenesis of signs and symptoms in affected patients, including severe mental retardation, ataxia, and excitotoxic seizures, remains unknown. To directly examine the role of ATP7A within the central nervous system, we generated Atp7a(Nes) mice, in which the Atp7a gene was specifically deleted within neural and glial cell precursors without impairing systemic copper homeostasis, and compared these mice with the mottled brindle (mo-br) mutant, a murine model of Menkes disease in which Atp7a is defective in all cells. Whereas mo-br mice displayed neurodegeneration, demyelination, and 100% mortality prior to weaning, the Atp7a(Nes) mice showed none of these phenotypes, exhibiting only mild sensorimotor deficits, increased anxiety, and susceptibility to NMDA-induced seizure. Our results indicate that the pathophysiology of severe neurological signs and symptoms in Menkes disease is the result of copper deficiency within the central nervous system secondary to impaired systemic copper homeostasis and does not arise from an intrinsic lack of ATP7A within the developing brain. Furthermore, the sensorimotor deficits, hypophagia, anxiety, and sensitivity to NMDA-induced seizure in the Atp7a(Nes) mice reveal unique autonomous requirements for ATP7A in the nervous system. Taken together, these data reveal essential roles for copper acquisition in the central nervous system in early development and suggest novel therapeutic approaches in affected patients. Copyright © 2015 the American Physiological Society.

An empirical model for global earthquake fatality estimation

USGS Publications Warehouse

Jaiswal, Kishor; Wald, David

2010-01-01

We analyzed mortality rates of earthquakes worldwide and developed a country/region-specific empirical model for earthquake fatality estimation within the U.S. Geological Survey's Prompt Assessment of Global Earthquakes for Response (PAGER) system. The earthquake fatality rate is defined as total killed divided by total population exposed at specific shaking intensity level. The total fatalities for a given earthquake are estimated by multiplying the number of people exposed at each shaking intensity level by the fatality rates for that level and then summing them at all relevant shaking intensities. The fatality rate is expressed in terms of a two-parameter lognormal cumulative distribution function of shaking intensity. The parameters are obtained for each country or a region by minimizing the residual error in hindcasting the total shaking-related deaths from earthquakes recorded between 1973 and 2007. A new global regionalization scheme is used to combine the fatality data across different countries with similar vulnerability traits.

Report of 3 Patients With Urea Cycle Defects Treated With Related Living-Donor Liver Transplant.

PubMed

Özçay, Figen; Barış, Zeren; Moray, Gökhan; Haberal, Nihan; Torgay, Adnan; Haberal, Mehmet

2015-11-01

Urea cycle defects are a group of metabolic disorders caused by enzymatic disruption of the urea cycle pathway, transforming nitrogen to urea for excretion from the body. Severe cases present in early infancy with life-threatening metabolic decompensation, and these episodes of hyperammonemia can be fatal or result in permanent neurologic damage. Despite the progress in pharmacologic treatment, long-term survival is poor especially for severe cases. Liver transplant is an alternative treatment option, providing sufficient enzymatic activity and decreasing the risk of metabolic decompensation. Three patients with urea cycle defects received related living-donor liver transplants at our hospital. Patients presented with late-onset ornithine transcarbamylase deficiency, argininosuccinate lyase deficiency, and citrullinemia. Maximum pretransplant ammonia levels were between 232 and 400 μmol/L (normal range is 18-72 μmol/L), and maximum posttransplant values were 52 to 94 μmol/L. All patients stopped medical treatment and dietary protein restriction for urea cycle defects after transplant. The patient with late-onset ornithine transcarbamylase deficiency already had motor deficits related to recurrent hyperammonemia attacks pretransplant. A major improvement could not be achieved, and he is wheelchair dependent at the age of 6 years. The other 2 patients had normal motor and mental skills before transplant, which have continued 12 and 14 months after transplant. Hepatic artery thrombosis in the patient with the ornithine transcarbamylase deficiency, intraabdominal infection in the patient with argininosuccinate lyase deficiency, and posterior reversible encephalopathy syndrome in the patient with citrullinemia were early postoperative complications. Histopathologic changes in livers explanted from patients with ornithine transcarbamylase deficiency and citrullinemia were nonspecific. The argininosuccinate lyase-deficient patient had portoportal fibrosis and cirrhotic nodule formation. In conclusion, liver transplant was a lifesaving procedure for our patients. Proper timing for transplant is important because high ammonia levels may result in permanent neurologic damage; however, transplant at younger ages also may increase morbidity.

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis.

PubMed

Rocca, Stefano; Schiavoni, Giovanna; Sali, Michela; Anfossi, Antonio Giovanni; Abalsamo, Laura; Palucci, Ivana; Mattei, Fabrizio; Sanchez, Massimo; Giagu, Anna; Antuofermo, Elisabetta; Fadda, Giovanni; Belardelli, Filippo; Delogu, Giovanni; Gabriele, Lucia

2013-01-01

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8⁻/⁻) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8⁻/⁻ mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8⁻/⁻, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8⁻/⁻ mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions.

Interferon Regulatory Factor 8-Deficiency Determines Massive Neutrophil Recruitment but T Cell Defect in Fast Growing Granulomas during Tuberculosis

PubMed Central

Sali, Michela; Anfossi, Antonio Giovanni; Abalsamo, Laura; Palucci, Ivana; Mattei, Fabrizio; Sanchez, Massimo; Giagu, Anna; Antuofermo, Elisabetta; Fadda, Giovanni; Belardelli, Filippo; Delogu, Giovanni; Gabriele, Lucia

2013-01-01

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions. PMID:23717393

Fatal autoimmunity results from the conditional deletion of Snai2 and Snai3

PubMed Central

Pioli, Peter D.; Chen, Xinjian; Weis, Janis J.; Weis, John H.

2015-01-01

Transcriptional regulation of gene expression is a key component of orchestrating proper immune cell development and function. One strategy for maintaining these transcriptional programs has been the evolution of transcription factor families with members possessing overlapping functions. Using the germ line deletion of Snai2 combined with the hematopoietic specific deletion of Snai3, we report that these factors function redundantly to preserve the development of B and T cells. Such animals display severe lymphopenia, alopecia and dermatitis as well as profound autoimmunity manifested by the production of high levels of autoantibodies as early as 3 weeks of age and die by 30 days after birth. Autoantibodies included both IgM and IgG isotypes and were reactive against cytoplasmic and membranous components. A regulatory T cell defect contributed to the autoimmune response in that adoptive transfer of wild type regulatory T cells alleviated symptoms of autoimmunity. Additionally, transplantation of Snai2/Snai3 double deficient bone marrow into Snai2 sufficient Rag2−/− recipients resulted in autoantibody generation. The results demonstrated that appropriate expression of Snai2 and Snai3 in cells of hematopoietic derivation plays an important role in development and maintenance of immune tolerance. PMID:25732600

Vascular calcification: When should we interfere in chronic kidney disease patients and how?

PubMed Central

Sharaf El Din, Usama Abdel Azim; Salem, Mona Mansour; Abdulazim, Dina Ossama

2016-01-01

Chronic kidney disease (CKD) patients are endangered with the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the fatalities. Cardiovascular calcifications affect most of the CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 and klotho deficiency were incriminated in the pathogenesis of vascular calcification through different mechanisms including their effects on endothelium and arterial wall smooth muscle cells. In addition, deficient klotho gene expression, a constant feature of CKD, promotes vascular pathology and shares in progression of the CKD. The role of gut in the etio-pathogenesis of systemic inflammation and vascular calcification is a newly discovered mechanism. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, different tools used to diagnose, the ideal timing to prevent or to withhold the progression of vascular calcification and the different medications and medical procedures that can help to prolong the survival of CKD patients. PMID:27648404

Reappraisal of known malaria resistance loci in a large multi-centre study

PubMed Central

Rockett, Kirk A.; Clarke, Geraldine M.; Fitzpatrick, Kathryn; Hubbart, Christina; Jeffreys, Anna E.; Rowlands, Kate; Craik, Rachel; Jallow, Muminatou; Conway, David J.; Bojang, Kalifa A.; Pinder, Margaret; Usen, Stanley; Sisay-Joof, Fatoumatta; Sirugo, Giorgio; Toure, Ousmane; Thera, Mahamadou A.; Konate, Salimata; Sissoko, Sibiry; Niangaly, Amadou; Poudiougou, Belco; Mangano, Valentina D.; Bougouma, Edith C.; Sirima, Sodiomon B.; Modiano, David; Amenga-Etego, Lucas N.; Ghansah, Anita; Koram, Kwadwo A.; Wilson, Michael D.; Enimil, Anthony; Evans, Jennifer; Amodu, Olukemi; Olaniyan, Subulade; Apinjoh, Tobias; Mugri, Regina; Ndi, Andre; Ndila, Carolyne M.; Uyoga, Sophie; Macharia, Alexander; Peshu, Norbert; Williams, Thomas N.; Manjurano, Alphaxard; Riley, Eleanor; Drakeley, Chris; Reyburn, Hugh; Nyirongo, Vysaul; Kachala, David; Molyneux, Malcolm; Dunstan, Sarah J.; Phu, Nguyen Hoan; Ngoc Quyen, Nguyen Thi; Thai, Cao Quang; Hien, Tran Tinh; Manning, Laurens; Laman, Moses; Siba, Peter; Karunajeewa, Harin; Allen, Steve; Allen, Angela; Davis, Timothy M. E.; Michon, Pascal; Mueller, Ivo; Green, Angie; Molloy, Sile; Johnson, Kimberly J.; Kerasidou, Angeliki; Cornelius, Victoria; Hart, Lee; Vanderwal, Aaron; SanJoaquin, Miguel; Band, Gavin; Le, Si Quang; Pirinen, Matti; Sepúlveda, Nuno; Spencer, Chris C.A.; Clark, Taane G.; Agbenyega, Tsiri; Achidi, Eric; Doumbo, Ogobara; Farrar, Jeremy; Marsh, Kevin; Taylor, Terrie; Kwiatkowski, Dominic P.

2015-01-01

Many human genetic associations with resistance to malaria have been reported but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. There was strong evidence of association with the HBB, ABO, ATP2B4, G6PD and CD40LG loci but previously reported associations at 22 other loci did not replicate in the multi-centre analysis. The large sample size made it possible to identify authentic genetic effects that are heterogeneous across populations or phenotypes, a striking example being the main African form of G6PD deficiency, which reduced the risk of cerebral malaria but increased the risk of severe malarial anaemia. The finding that G6PD deficiency has opposing effects on different fatal complications of P. falciparum infection indicates that the evolutionary origins of this common human genetic disorder are more complex than previously supposed. PMID:25261933

Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL

PubMed Central

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-01-01

Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL. PMID:19385065

Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

PubMed

von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

2009-05-01

Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

Case report: Ribavirin and vitamin A in a severe case of measles

PubMed Central

Bichon, Amandine; Aubry, Camille; Benarous, Lucas; Drouet, Hortense; Zandotti, Christine; Parola, Philippe; Lagier, Jean-Christophe

2017-01-01

Abstract Rationale: Despite a vaccine being widely available, measles continues to occur frequently, with sometimes lethal consequences. Patients concerns: The mortality rate reaches 35% and measles represents 44% of the 1.4 million deaths which are due to preventable diseases. Severe forms of measles are reported, mainly in young, unvaccinated adults, and in specific populations. The risk factors for severe measles include no or incomplete vaccination and vitamin A deficiency. Apart from secondary measles-related infections, severe measles is mainly represented by neurological, respiratory, and digestive symptoms. Diagnoses: Strengthening the hypothesis that there is a link between vitamin A deficiency and severe measles in this paper we report the case of a 25-year-old unvaccinated man hospitalized for severe and complicated measles. Outcomes: The evolution was good after administration of intramuscular vitamin A as well as intravenous ribavirin. Lessons: Measles remains a fatal and serious disease. The early use of ribavirin and vitamin A shows significant improvements regarding morbimortality and should be systematic in severe cases. PMID:29390321

Surveillance of traumatic firefighter fatalities: an assessment of four systems.

PubMed

Estes, Chris R; Marsh, Suzanne M; Castillo, Dawn N

2011-01-01

Firefighters regularly respond to hazardous situations that put them at risk for fatal occupational injuries. Traumatic occupational fatality surveillance is a foundation for understanding the problem and developing prevention strategies. We assessed four surveillance systems for their utility in characterizing firefighter fatalities and informing prevention measures. We examined three population-based systems (the Bureau of Labor Statistics' Census of Fatal Occupational Injuries and systems maintained by the United States Fire Administration and the National Fire Protection Association) and one case-based system (data collected through the National Institute for Occupational Safety and Health Fire Fighter Fatality Investigation and Prevention Program). From each system, we selected traumatic fatalities among firefighters for 2003-2006. Then we compared case definitions, methods for case ascertainment, variables collected, and rate calculation methods. Overall magnitude of fatalities differed among systems. The population-based systems were effective in characterizing the circumstances of traumatic firefighter fatalities. The case-based surveillance system was effective in formulating detailed prevention recommendations, which could not be made based on the population-based data alone. Methods for estimating risk were disparate and limited fatality rate comparisons between firefighters and other workers. The systems included in this study contribute toward a greater understanding of firefighter fatalities. Areas of improvement for these systems should continue to be identified as they are used to direct research and prevention efforts.

A statistical analysis of the global historical volcanic fatalities record

USGS Publications Warehouse

Auker, Melanie Rose; Sparks, Robert Stephen John; Siebert, Lee; Crosweller, H. S.; Ewert, John W.

2013-01-01

A new database of volcanic fatalities is presented and analysed, covering the period 1600 to 2010 AD. Data are from four sources: the Smithsonian Institution, Witham (2005), CRED EM-DAT and Munich RE. The data were combined and formatted, with a weighted average fatality figure used where more than one source reports an event; the former two databases were weighted twice as strongly as the latter two. More fatal incidents are contained within our database than similar previous works; approximately 46% of the fatal incidents are listed in only one of the four sources, and fewer than 10% are in all four. 278,880 fatalities are recorded in the database, resultant from 533 fatal incidents. The fatality count is dominated by a handful of disasters, though the majority of fatal incidents have caused fewer than ten fatalities. Number and empirical probability of fatalities are broadly correlated with VEI, but are more strongly influenced by population density around volcanoes and the occurrence and extent of lahars (mudflows) and pyroclastic density currents, which have caused 50% of fatalities. Indonesia, the Philippines, and the West Indies dominate the spatial distribution of fatalities, and there is some negative correlation between regional development and number of fatalities. With the largest disasters removed, over 90% of fatalities occurred between 5 km and 30 km from volcanoes, though the most devastating eruptions impacted far beyond these distances. A new measure, the Volcano Fatality Index, is defined to explore temporal changes in societal vulnerability to volcanic hazards. The measure incorporates population growth and recording improvements with the fatality data, and shows prima facie evidence that vulnerability to volcanic hazards has fallen during the last two centuries. Results and interpretations are limited in scope by the underlying fatalities data, which are affected by under-recording, uncertainty, and bias. Attempts have been made to estimate the extent of these issues, and to remove their effects where possible.The data analysed here are provided as supplementary material. An updated version of the Smithsonian fatality database fully integrated with this database will be publicly available in the near future and subsequently incorporate new data.

Phosphatidylinositol 3-kinase inhibition restores Ca2+ release defects and prolongs survival in myotubularin-deficient mice

PubMed Central

Kutchukian, Candice; Lo Scrudato, Mirella; Tourneur, Yves; Poulard, Karine; Vignaud, Alban; Berthier, Christine; Allard, Bruno; Lawlor, Michael W.; Buj-Bello, Ana; Jacquemond, Vincent

2016-01-01

Mutations in the gene encoding the phosphoinositide 3-phosphatase myotubularin (MTM1) are responsible for a pediatric disease of skeletal muscle named myotubular myopathy (XLMTM). Muscle fibers from MTM1-deficient mice present defects in excitation–contraction (EC) coupling likely responsible for the disease-associated fatal muscle weakness. However, the mechanism leading to EC coupling failure remains unclear. During normal skeletal muscle EC coupling, transverse (t) tubule depolarization triggers sarcoplasmic reticulum (SR) Ca2+ release through ryanodine receptor channels gated by conformational coupling with the t-tubule voltage-sensing dihydropyridine receptors. We report that MTM1 deficiency is associated with a 60% depression of global SR Ca2+ release over the full range of voltage sensitivity of EC coupling. SR Ca2+ release in the diseased fibers is also slower than in normal fibers, or delayed following voltage activation, consistent with the contribution of Ca2+-gated ryanodine receptors to EC coupling. In addition, we found that SR Ca2+ release is spatially heterogeneous within myotubularin-deficient muscle fibers, with focally defective areas recapitulating the global alterations. Importantly, we found that pharmacological inhibition of phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity rescues the Ca2+ release defects in isolated muscle fibers and increases the lifespan and mobility of XLMTM mice, providing proof of concept for the use of PtdIns 3-kinase inhibitors in myotubular myopathy and suggesting that unbalanced PtdIns 3-kinase activity plays a critical role in the pathological process. PMID:27911767

Fuzzy logic inference-based Pavement Friction Management and real-time slippery warning systems: A proof of concept study.

PubMed

Najafi, Shahriar; Flintsch, Gerardo W; Khaleghian, Seyedmeysam

2016-05-01

Minimizing roadway crashes and fatalities is one of the primary objectives of highway engineers, and can be achieved in part through appropriate maintenance practices. Maintaining an appropriate level of friction is a crucial maintenance practice, due to the effect it has on roadway safety. This paper presents a fuzzy logic inference system that predicts the rate of vehicle crashes based on traffic level, speed limit, and surface friction. Mamdani and Sugeno fuzzy controllers were used to develop the model. The application of the proposed fuzzy control system in a real-time slippery road warning system is demonstrated as a proof of concept. The results of this study provide a decision support model for highway agencies to monitor their network's friction and make appropriate judgments to correct deficiencies based on crash risk. Furthermore, this model can be implemented in the connected vehicle environment to warn drivers of potentially slippery locations. Published by Elsevier Ltd.

Fluorescence Lifetime Imaging of Physiological Free Cu(II) Levels in Live Cells with a Cu(II)-Selective Carbonic Anhydrase-Based Biosensor

PubMed Central

McCranor, Bryan J.; Szmacinski, Henryk; Zeng, Hui Hui; Stoddard, A.K.; Hurst, Tamiika; Fierke, Carol A.; Lakowicz, J.R.

2014-01-01

Copper is a required trace element that plays key roles in a number of human enzymes, such that copper deficiency or genetic defects in copper transport lead to serious or fatal disease. Rae, et al., had famously predicted that free copper ion levels in the cell cytoplasm were extremely low, typically too low to be observable. We recently developed a variant of human apocarbonic anhydrase II for sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in the presence of ordinary cellular (picomolar) concentrations of free zinc. We inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic anhydrase into PC-12 cells and found that the levels are indeed extremely low (in the femtomolar range). We imaged the free Cu(II) levels in living cells by means of frequency-domain fluorescence lifetime microscopy. Implications of this finding are discussed. PMID:24671220

Immunization of knock-out α/β interferon receptor mice against high lethal dose of Crimean-Congo hemorrhagic fever virus with a cell culture based vaccine.

PubMed

Canakoglu, Nurettin; Berber, Engin; Tonbak, Sukru; Ertek, Mustafa; Sozdutmaz, Ibrahim; Aktas, Munir; Kalkan, Ahmet; Ozdarendeli, Aykut

2015-03-01

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease. The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia. During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in humans with fatality rates up to 30%. Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved. Lately, IFN α/β receptor deficient (IFNAR-/-) mice have been established as a novel small animal model of CCHF virus infection. In the present study, we found that IFNAR-/- mice highly susceptible to CCHF virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine elicited a significant level of protection against high dose challenge (1,000 PPFU) with a homologous CCHF virus in IFNAR-/- mice.

Inborn oxidative phosphorylation defect as risk factor for propofol infusion syndrome.

PubMed

Vanlander, A V; Jorens, P G; Smet, J; De Paepe, B; Verbrugghe, W; Van den Eynden, G G; Meire, F; Pauwels, P; Van der Aa, N; Seneca, S; Lissens, W; Okun, J G; Van Coster, R

2012-04-01

Propofol is an anesthetic agent widely used for induction and maintenance of anesthesia, and sedation in children. Although generally considered as reliable and safe, administration of propofol can occasionally induce a potentially fatal complication known as propofol infusion syndrome (PRIS). Mitochondrial dysfunction has been implicated in the pathogenesis of PRIS. We report on an adult patient with Leber hereditary optic neuropathy (LHON) who developed PRIS. He was a carrier of the m.3460G>A mutation, one of the major three pathogenic point mutations associated with LHON. The propositus was blind and underwent propofol sedation after severe head injury. Five days after start of propofol infusion, the patient died. The activity of complex I of the oxidative phosphorylation (OXPHOS) system was severely deficient in skeletal muscle. Our observation indicates that fulminate PRIS can occur in an adult patient with an inborn OXPHOS defect and corroborates the hypothesis that PRIS is caused by inhibition of the OXPHOS system. © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

Genotypes and clinical phenotypes in children with cytochrome-c oxidase deficiency.

PubMed

Darin, N; Moslemi, A-R; Lebon, S; Rustin, P; Holme, E; Oldfors, A; Tulinius, M

2003-12-01

Cytochrome c oxidase (COX) deficiency has been associated with a wide spectrum of clinical features and may be caused by mutations in different genes of both the mitochondrial and the nuclear DNA. In an attempt to correlate the clinical phenotype with the genotype in 16 childhood cases, mtDNA was analysed for deletion, depletion, and mutations in the three genes encoding COX subunits and the 22 tRNA genes. Furthermore, nuclear DNA was analysed for mutations in the SURF1, SCO2, COX10, and COX17 genes and cases with mtDNA depletion were analysed for mutations in the TK2 gene. SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp) gene was identified in the fourth. One case with mtDNA depletion had mutations in the TK2 gene. In two cases with leukoencephalopathy, one case with encephalopathy, five cases with fatal infantile myopathy and cardiomyopathy, two cases with benign infantile myopathy, and one case with mtDNA depletion, no mutations were identified. We conclude that COX deficiency in childhood should be suspected in a wide range of clinical settings and although an increasing number of genetic defects have been identified, the underlying mutations remain unclear in the majority of the cases.

Il-10 deficient mice express IFN-γ mRNA and clear Leptospira interrogans from their kidneys more rapidly than normal C57BL/6 mice.

PubMed

Devlin, Amy A; Halvorsen, Priya J; Miller, Jennifer C; Laster, Scott M

2017-05-01

Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease. To test this hypothesis we have compared bacteremia and the cytokine response of normal and IL-10 deficient C57Bl/6 mice following ip infection with L. interrogans. In normal mice bacterial 16s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7days after infection. In contrast, in IL-10 deficient mice, the organism was eliminated more rapidly from the kidney. We found that infection of both control and IL-10 deficient mice produced similar levels of a number of pro-inflammatory cytokine mRNAs. On the other hand, IFN-γ mRNA was only induced in IL-10 deficient mice. These results support the hypothesis that L. interrogans ability to induce IL-10, which in turn prevents production of IFN-γ and inhibits T cell immunity, may contribute to the persistent growth of this microorganism in the murine kidney. Copyright © 2017 Elsevier GmbH. All rights reserved.

Smeed's law and expected road fatality reduction: An assessment of the Italian case.

PubMed

Persia, Luca; Gigli, Roberto; Usami, Davide Shingo

2015-12-01

Smeed's law defines the functional relationship existing between the fatality rate and the motorization rate.While focusing on the Italian case and based on the Smeed's law, the study assesses the possibility for Italy of reaching the target of halving the number of road fatalities by 2020, in light of the evolving socioeconomic situation. A Smeed's model has been calibrated based on the recorded Italian data. The evolution of the two indicators, fatality and motorization rates, has been estimated using the predictions of the main parameters (population, fleet size and fatalities). Those trends have been compared with the natural decreasing trend derived from the Smeed's law. Nine scenarios have been developed showing the relationship between the fatality rate and the motorization rate. In case of a limited increase (logistic regression) of the vehicle fleet and according to the estimated evolution of the population, the path defined by motorization and fatality rate is very steep, diverging from the estimated confidence interval of the Smeed's model. In these scenarios the motorization rate is almost constant during the decade. In the actual economic context, a limited development of the vehicle fleet is more plausible. In these conditions the target achievement of halving the number of fatalities in Italy may occur only in case of a structural break (i.e., the introduction of highly effective road safety policies). Practical application: The proposed tools can be used both to evaluate retrospectively the effectiveness of road safety improvements and to assess if a relevant effort is needed to reach the established road safety targets.

Reported fatal and non-fatal incidents involving tourists in Hawaii Volcanoes National Park, 1992-2002.

PubMed

Heggie, Travis W

2005-08-01

Objectives. To examine fatal and non-fatal incidents involving tourists in Hawaii Volcanoes National Park. Methods. Official press releases from the public relations office at Hawaii Volcanoes National Park were examined for reports of fatal and non-fatal incidents involving tourists. Results. Between 1992 and 2002 there were 65 press releases reporting 40 fatalities, 45 serious injuries, 53 minor injuries, and 25 no injury events. Severity information was unavailable for four additional tourists. Aircraft and backcountry incidents each accounted for 30% of all incidents followed by road incidents (22%) and frontcountry incidents (17%). Aircraft incidents reported 17 fatalities, backcountry incidents accounted for 10 fatalities, frontcountry incidents reported seven fatalities, and road incidents totaled six fatalities. One fatality was classified as a suicide. Backcountry (23) and road (10) incidents had the highest number of serious incidents. Male tourists (62) were more frequently involved in incidents than female tourists (41) and tourists aged 20-29 years and 40-49 years accounted for the highest number of fatalities and total incidents. Conclusions. Helicopter tours, hiking in areas with active lava flows, falls into steam vents and earthcracks, and driving unfamiliar rental cars in unfamiliar locations are the major activities resulting in death and serious injury. Additional factors such as tourists ignoring warning signs, wandering off-trail or hiking at night, tourists misinformed by guidebooks and other tourists, and tourists with pre-existing heart and asthma conditions are contributing causes in many incidents. The findings of this study provide information that allows prospective tourists, tourism managers, and travel health providers make informed decisions that promote safe tourism and can aid future efforts in developing preventative strategies at tourist destinations with similar environments and activities. However, in order for preventative strategies to be most effective, future research using medical or emergency response records and employing an injury epidemiology framework that identifies the cause of fatal and non-fatal injuries is recommended.

[Fatal occupational accidents in Lombardy].

PubMed

Pianosi, G

1995-01-01

All fatal occupational accidents compensated in Lombardy from 1984 to 1989 were analyzed (1259 cases): significant differences between geographical distribution of fatal occupational accidents and workers were observed. Males accounted for about 95% of fatalities; an excess of cases was shown in both young and elderly workers. Death was the consequence of injuries involving most frequently the head, thorax and spinal cord. An excess of fatalities was observed in agriculture and, at a lower level, in manufacturing industries; small enterprises were involved in approximately 25% of fatalities occurring in the manufacturing industries and services. Employers were the victims of fatal accidents in 50% of cases in agriculture and in 70% of cases in craft industries. Construction, agriculture and transport accounted for about 50% of all fatalities. About 50% of fatal occupational accidents were related to vehicle use: the victim was the driver in the majority of cases, sometimes the victim was run over by a vehicle or fell from a vehicle. The results agree with some previous observations (e.g.: sex and age distribution; construction, agriculture and transport as working activities at high accident risk); but some original observations have emerged, in particular about the frequency of employers as victims and the role of vehicles in the genesis of fatal occupational accidents. If further studies confirm these latter observations, important developments could follow in preventive action design and implementation.

Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

PubMed Central

Marques, Paul R

2013-01-01

Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sidhu, Navdeep S.; University of Göttingen, Tammannstrasse 4, 37077 Göttingen; Schreiber, Kathrin

2014-05-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However,more » the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.« less

Estimating Casualties for Large Earthquakes Worldwide Using an Empirical Approach

USGS Publications Warehouse

Jaiswal, Kishor; Wald, David J.; Hearne, Mike

2009-01-01

We developed an empirical country- and region-specific earthquake vulnerability model to be used as a candidate for post-earthquake fatality estimation by the U.S. Geological Survey's Prompt Assessment of Global Earthquakes for Response (PAGER) system. The earthquake fatality rate is based on past fatal earthquakes (earthquakes causing one or more deaths) in individual countries where at least four fatal earthquakes occurred during the catalog period (since 1973). Because only a few dozen countries have experienced four or more fatal earthquakes since 1973, we propose a new global regionalization scheme based on idealization of countries that are expected to have similar susceptibility to future earthquake losses given the existing building stock, its vulnerability, and other socioeconomic characteristics. The fatality estimates obtained using an empirical country- or region-specific model will be used along with other selected engineering risk-based loss models for generation of automated earthquake alerts. These alerts could potentially benefit the rapid-earthquake-response agencies and governments for better response to reduce earthquake fatalities. Fatality estimates are also useful to stimulate earthquake preparedness planning and disaster mitigation. The proposed model has several advantages as compared with other candidate methods, and the country- or region-specific fatality rates can be readily updated when new data become available.

Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.

PubMed

Sleat, D E; Donnelly, R J; Lackland, H; Liu, C G; Sohar, I; Pullarkat, R K; Lobel, P

1997-09-19

Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease whose defective gene has remained elusive. A molecular basis for LINCL was determined with an approach applicable to other lysosomal storage diseases. When the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, a single protein was identified that is absent in LINCL. Sequence comparisons suggest that this protein is a pepstatin-insensitive lysosomal peptidase, and a corresponding enzymatic activity was deficient in LINCL autopsy specimens. Mutations in the gene encoding this protein were identified in LINCL patients but not in normal controls.

Fatality analysis reporting system and roadway inventory correlation.

DOT National Transportation Integrated Search

2013-01-01

In this project, we developed an integrated database to provide new analysis capabilities : for discovering correlations between roadway characteristics and the occurrence of : fatality collisions. Specifically, the aim of this data analysis project ...

Genetic basis for correction of very-long-chain acyl-coenzyme A dehydrogenase deficiency by bezafibrate in patient fibroblasts: toward a genotype-based therapy.

PubMed

Gobin-Limballe, S; Djouadi, F; Aubey, F; Olpin, S; Andresen, B S; Yamaguchi, S; Mandel, H; Fukao, T; Ruiter, J P N; Wanders, R J A; McAndrew, R; Kim, J J; Bastin, J

2007-12-01

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an inborn mitochondrial fatty-acid beta-oxidation (FAO) defect associated with a broad mutational spectrum, with phenotypes ranging from fatal cardiopathy in infancy to adolescent-onset myopathy, and for which there is no established treatment. Recent data suggest that bezafibrate could improve the FAO capacities in beta-oxidation-deficient cells, by enhancing the residual level of mutant enzyme activity via gene-expression stimulation. Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, we investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblasts representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 h) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. This pattern of response was not due to differential inductions of VLCAD messenger RNA, as shown by quantitative real-time polymerase chain reaction, but reflected variable increases in measured VLCAD residual enzyme activity in response to bezafibrate. Genotype cross-analysis allowed the identification of alleles carrying missense mutations, which could account for these different pharmacological profiles and, on this basis, led to the characterization of 9 mild and 11 severe missense mutations. Altogether, the responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype, thus providing a new approach for analysis of genetic heterogeneity. Finally, this study emphasizes the potential of bezafibrate, a widely prescribed hypolipidemic drug, for the correction of VLCAD deficiency and exemplifies the integration of molecular information in a therapeutic strategy.

The Development of a White Water Rafting Code of Practice in Response to Multiple Fatalities in Queensland: How Will It Impact the Commercial and Educational Sector?

ERIC Educational Resources Information Center

Murray, Sean

2015-01-01

In this article I review lessons to be learned from five commercial rafting participant fatalities in Northern Queensland between 2007 and 2009, and examine some implications of the coroner's recommendations from an outdoor education perspective. I aim both to help prevent future fatalities and to contribute to discussion about how best to achieve…

Dystrophin-deficient large animal models: translational research and exon skipping

PubMed Central

Yu, Xinran; Bao, Bo; Echigoya, Yusuke; Yokota, Toshifumi

2015-01-01

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder caused by mutations in the dystrophin gene. Affecting approximately 1 in 3,600-9337 boys, DMD patients exhibit progressive muscle degeneration leading to fatality as a result of heart or respiratory failure. Despite the severity and prevalence of the disease, there is no cure available. While murine models have been successfully used in illustrating the mechanisms of DMD, their utility in DMD research is limited due to their mild disease phenotypes such as lack of severe skeletal muscle and cardiac symptoms. To address the discrepancy between the severity of disease displayed by murine models and human DMD patients, dystrophin-deficient dog models with a splice site mutation in intron 6 were established. Examples of these are Golden Retriever muscular dystrophy and beagle-based Canine X-linked muscular dystrophy. These large animal models are widely employed in therapeutic DMD research due to their close resemblance to the severity of human patient symptoms. Recently, genetically tailored porcine models of DMD with deleted exon 52 were developed by our group and others, and can potentially act as a new large animal model. While therapeutic outcomes derived from these large animal models can be more reliably extrapolated to DMD patients, a comprehensive understanding of these models is still needed. This paper will discuss recent progress and future directions of DMD studies with large animal models such as canine and porcine models. PMID:26396664

Fatalism and its implications for risky road use and receptiveness to safety messages: a qualitative investigation in Pakistan.

PubMed

Kayani, A; King, M J; Fleiter, J J

2012-12-01

Given the increasing vehicle numbers and expanding road construction in developing countries, the importance of safe road user behaviour is critical. Road traffic crashes (RTCs) are a significant problem in Pakistan; however, the factors that contribute to RTCs in Pakistan are not well researched. Fatalistic beliefs are a potential barrier to the enhancement of road safety, especially participation in health-promoting and injury prevention behaviours, and also contribute to risk taking. Fatalistic beliefs relating to road safety have been found in some developing countries, although research is scarce and indicates that the nature and extent of fatalism differs in each country. Qualitative research was undertaken with a range of drivers, religious orators, police and policy makers to explore associations between fatalism, risky road use and associated issues. Findings indicate that fatalistic beliefs are pervasive in Pakistan, are strongly linked with religion, present a likely barrier to road safety messages and contribute to risky road use. Fatalism appears to be a default attribution of RTC and the intensity of belief in fate surpasses the kinds of fatalism noted in the limited existing literature. These findings have importance to developing road safety countermeasures in countries where fatalistic beliefs are strong.

Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune system?

PubMed

Baize, S; Leroy, E M; Mavoungou, E; Fisher-Hoch, S P

2000-02-01

In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. While data suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal cases, experimental Ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both T and B cells. Nevertheless, we are able to conclude from the accumulated evidence that early interactions between Ebola virus and the immune system, probably via macrophages, main targets for viral replication, lead to massive destruction of immune cells in fatal cases.

A study of fatal pedestrian crashes at rural low-volume road intersections in southwest China.

PubMed

Xie, Xiaoli; Nikitas, Alexandros; Liu, Hongqi

2018-04-03

Although intersections correspond to a small proportion of the entire roadway system, they account for a disproportionally high number of fatal pedestrian crashes, especially on rural roads situated in low- and middle-income countries. This article examines pedestrian safety at rural intersections and suggests applicable accident prevention treatments by providing an in-depth analysis of 28 fatal pedestrian crashes from 8 low-volume roads in southwest China. The driving reliability and error analysis method (DREAM) is a method to support a systematic classification of accident causation information and to facilitate aggregation of that information into patterns of contributing factors. This is the first time that DREAM was used to analyze pedestrian-vehicle crashes and provide suggestions for road improvements in China. The key issues adversely affecting pedestrian safety can be organized in 4 distinctive thematic categories, namely, deficient intersection safety infrastructure, lack of pedestrian safety education, inadequate driver training, and insufficient traffic law enforcement. Given that resources for traffic safety investments in rural areas are limited, it is determined that the potential countermeasures should focus on low-cost, easily implementable, and long-lasting measures increasing the visibility and predictability of pedestrian movement and reducing speeding and irresponsible driving among drivers and risk-taking behaviors among pedestrians. Accident prevention treatments are suggested based on their suitability for rural areas in southwest China. These countermeasures include introducing better access management and traffic calming treatments, providing more opportunities for pedestrian education, and enhancing the quality of driver training and traffic law enforcement.

Sharp Force Injuries at the University Hospital of the West Indies, Kingston, Jamaica: A Seventeen-year Autopsy Review.

PubMed

Neblett, A; Williams, N P

2014-09-01

This study aimed to ascertain the prevalence and patterns of fatal sharp force injuries, victims' demographics, cause of death and average survival time at the University Hospital of the West Indies (UHWI), Kingston, Jamaica. The autopsy records for 1990-2010 were searched for fatal cases of sharp force injuries. The records for 1998-2001 were not located. A 17-year retrospective analysis was therefore performed and findings for the two periods, 1990-1997 and 2002-2010 were compared. All data were obtained from the provisional anatomical diagnoses (PAD) autopsy reports. During the 17-year period, 57/4264 autopsies were performed for sharp force injuries, yielding an overall autopsy prevalence rate of 1.34% (1.25%, 26/2086 (95% CI 0.77, 1.73) in Period 1 and 1.42%, 31/2178 (95% CI 0.92, 1.92) in Period 2). The majority were males (91.1%), in the age group 15-39 years (77%), mean age of 30.9 years (range = 17─65 years). Stab wounds predominated (91.3%) and the chest was the area most frequently stabbed (42.1%). In the 24 fatalities due to chest injuries only, eight (33.3%) had injuries to the heart alone. Forty-five patients (79.0%) died within 24 hours from exsanguination. Injury documentation at autopsy was deficient. Stabbing was the most common sharp force injury, mainly involving the chest and young men were at greatest risk. Most patients died from exsanguination within 24 hours of admission. Introduction of synoptic-type reports for both clinical and autopsy examination may improve documentation.

Occupational accidents in Russia and the Russian Arctic.

PubMed

Dudarev, Alexey A; Karnachev, Igor P; Odland, Jon Øyvind

2013-01-01

According to official statistics, the rate of occupational accidents (OAs) and fatal injuries in Russia decreased about 5-fold and 2-fold, respectively, from 1975 to 2010, but working conditions during this period had the opposite trend; for example, the number of people who work in unfavourable and hazardous conditions (particularly since 1991) has increased significantly. This review summarises the results of a search of the relevant peer-reviewed literature published in Russia and official statistics on OAs and occupational safety in Russia and the Russian Arctic in 1980-2010. The occupational safety system in Russia has severely deteriorated in the last 2 decades, with legislators tending to promote the interests of industry and business, resulting in the neglect of occupational safety and violation of workers' rights. The majority of workers are employed in conditions that do not meet rules of safety and hygiene. More than 60% of OAs can be attributed to management practices--violation of safety regulations, poor organisation of work, deficiency of certified occupational safety specialists and inadequate personnel training. Research aimed at improving occupational safety and health is underfunded. There is evidence of widespread under-reporting of OAs, including fatal accidents. Three federal agencies are responsible for OAs recording; their data differ from each other as they use different methodologies. The rate of fatal OAs in Russia was 3-6 times higher than in Scandinavian countries and about 2 times higher compared to United States and Canada in 2001. In some Russian Arctic regions OAs levels are much higher. Urgent improvement of occupational health and safety across Russia, especially in the Arctic regions, is needed.

Ghrelin and the cardiovascular system.

PubMed

Tokudome, Takeshi; Kishimoto, Ichiro; Miyazato, Mikiya; Kangawa, Kenj

2014-01-01

Ghrelin is a peptide that was originally isolated from the stomach. It exerts potent growth hormone (GH)-releasing and orexigenic activities. Several studies have highlighted the therapeutic benefits of ghrelin for the treatment of cardiovascular disease. In animal models of chronic heart failure, the administration of ghrelin improved cardiac function and remodeling; these findings were replicated in human patients with heart failure. Moreover, in an animal study, ghrelin administration effectively reduced pulmonary hypertension induced by chronic hypoxia. In addition, repeated administration of ghrelin to cachectic patients with chronic obstructive pulmonary disease had positive effects on overall body function, including muscle wasting, functional capacity and sympathetic activity. The administration of ghrelin early after myocardial infarction (MI) reduced fatal arrhythmia and related mortality. In ghrelin-deficient mice, both exogenous and endogenous ghrelin were protective against fatal arrhythmia and promoted remodeling after MI. Although the mechanisms underlying the effects of ghrelin on the cardiovascular system remain unclear, there are indications that its beneficial effects are mediated through both direct physiological actions, including increased GH levels, improved energy balance and direct actions on cardiovascular cells, and regulation of autonomic nervous system activity. Therefore, ghrelin is a promising novel therapeutic agent for cardiovascular disease. © 2014 S. Karger AG, Basel.

Clinical epidemiology of HIV/AIDS in China from 2004-2011.

PubMed

Li, Min; Shen, Yinzhong; Jiang, Xiaofei; Li, Qi; Zhou, Xiaoming; Lu, Hongzhou

2014-02-01

This study retrospectively analyzed Chinese publicly reported data on Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS). The HIV/AIDS morbidity (1/100,000) and mortality (1/100,000) rates in China continually increased from 0.23 and 0.06 in 2004 to 1.53 and 0.69 in 2011, respectively. The AIDS case fatality rate decreased yearly from 53.57% in 2008 to 45.11% in 2011, and the fatality rate in rural areas (0.25-0.42%) was higher than that in cities (0.13-0.22%). The number of HIV/AIDS patients discharged from city-level hospitals increased from 329 in 2004 to 7,266 in 2011, and this number was higher than the number of similar patients discharged from county-level (rural) hospitals (the number of HIV/AIDS patients increased from 252 in 2004 to 5,957 in 2011). The factors contributing to these trends include: enhanced physician HIV/AIDS education regarding diagnosis, intervention, monitoring, testing, and treatment; improved safety of blood collection and use; and improved management of HIV/AIDS patients. Therefore, HIV/AIDS prevention and control in rural areas of China is the key to reducing HIV transmission and mortality in China.

Unintended shootings in a large metropolitan area: an incident-based analysis.

PubMed

Ismach, Richard B; Reza, Avid; Ary, Roy; Sampson, Tomoko Rie; Bartolomeos, Kidist; Kellermann, Arthur L

2003-01-01

We determine the proportion of unintended shootings that might be prevented by promoting safe storage, safe handling, and/or safer firearm designs. A regional firearm injury surveillance system was used to identify fatal and nonfatal unintentional shootings in a 5-county metropolitan area. Case reports were reviewed, and the causes of each shooting were independently classified by 4 members of the research team. A consensus conference was held to resolve disagreements. Between May 1, 1996, and June 30, 2000, 216 cases of unintentional firearm injury were identified, 3.8% of the shootings documented during the study period. Six (2.8%) were fatal. The majority of victims were between 15 and 34 years of age. One fourth (54) of the shootings involved victims younger than 18 years. Handguns were involved in 87% of the incidents. Enough information was available to characterize the incident in 122 (57%) cases. All but 6 fell into 1 or more of 3 broad categories of causation: Child access (14%), mishandling (74%), and/or deficiencies in firearm design (32%). Many unintentional shootings could be prevented by promoting safe storage of guns in the home, promoting safe handling of firearms, and requiring that all new handguns incorporate basic safety features.

A novel deficiency of mitochondrial ATPase of nuclear origin.

PubMed

Houstek, J; Klement, P; Floryk, D; Antonická, H; Hermanská, J; Kalous, M; Hansíková, H; Hout'ková, H; Chowdhury, S K; Rosipal, T; Kmoch, S; Stratilová, L; Zeman, J

1999-10-01

We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase). A hypotrophic newborn from a consanguineous marriage presented severe lactic acidosis, cardiomegaly and hepatomegaly and died from heart failure after 2 days. The activity of oligomycin-sensitive ATPase was only 31-34% of the control, both in muscle and heart, but the activities of cytochrome c oxidase, citrate synthase and pyruvate dehydrogenase were normal. Electrophoretic and western blot analysis revealed selective reduction of ATPase complex but normal levels of the respiratory chain complexes I, III and IV. The same selective deficiency of ATPase was found in cultured skin fibroblasts which showed similar decreases in ATPase content, ATPase hydrolytic activity and level of substrate-dependent ATP synthesis (20-25, 18 and 29-33% of the control, respectively). Pulse-chase labelling of patient fibroblasts revealed low incorporation of [(35)S]methionine into assembled ATPase complexes, but increased incorporation into immunoprecipitated ATPase subunit beta, which had a very short half-life. In contrast, no difference was found in the size and subunit composition of the assembled and newly produced ATPase complex. Transmitochondrial cybrids prepared from enucleated fibroblasts of the patient and rho degrees cells derived from 143B. TK(-)human osteosarcoma cells fully restored the ATPase activity, ATP synthesis and ATPase content, when compared with control cybrids. Likewise, the pattern of [(35)S]methionine labelling of ATPase was found to be normal in patient cybrids. We conclude that the generalized deficiency of mitochondrial ATPase described is of nuclear origin and is caused by altered biosynthesis of the enzyme.

Adult classical homocystinuria requiring parenteral nutrition: Pitfalls and management.

PubMed

Tran, Christel; Bonafé, Luisa; Nuoffer, Jean-Marc; Rieger, Julie; Berger, Mette M

2017-07-25

Homocystinuria due to cystathionine beta synthase (CBS) deficiency presents with a wide clinical spectrum. Treatment by the enteral route aims at reducing homocysteine levels by using vitamin B6, possibly methionine-restricted diet, betaine and/or folate and vitamin B 12 supplementation. Currently no nutritional guidelines exist regarding parenteral nutrition (PN) under acute conditions. Exhaustive literature search was performed, in order to identify the relevant studies describing the pathogenesis and nutritional intervention of adult classical homocystinuria requiring PN. Description of an illustrative case of an adult female with CBS deficiency and intestinal perforation, who required total PN due to contraindication to enteral nutrition. Nutritional management of decompensated classical homocystinuria is complex and currently no recommendation exists regarding PN composition. Amino acid profile and monitoring of total homocysteine concentration are the main tools enabling a precise assessment of the severity of metabolic alterations. In case of contraindication to enteral nutrition, compounded PN will be required, as described in this paper, to ensure adequate low amounts of methionine and others essential amino acids and avoid potentially fatal toxic hypermethioninemia. By reviewing the literature and reporting successful nutritional management of a decompensated CBS deficiency using tailored PN with limited methionine intake and n-3 PUFA addition, we would like to underscore the fact that standard PN solutions are not adapted for CBS deficient critical ill patients: new solutions are required. High methionine levels (>800 μmol/L) being potentially neurotoxic, there is an urgent need to improve our knowledge of acute nutritional therapy. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Fatal Occupational Injuries among Non-governmental Employees in Malaysia

PubMed Central

Abas, Adinegara bin Lutfi; Mohd Said, Datuk Abd. Razzak B.; Aziz Mohammed, Mohammed Azman B.; Sathiakumar, Nalini

2012-01-01

Background In Malaysia, surveillance of fatal occupational injuries is fragmented. We therefore analyzed an alternative data source from Malaysia’s Social Security organization, the PERKESO. Methods We conducted a secondary data analysis of the PERKESO database comprised of 7 million employees from 2002 to 2006. Results Overall, the average annual incidence was 9.2 fatal occupational injuries per 100,000 workers. During the five-year period, there was a decrease in the absolute number of fatal injuries by 16% and the incidence by 34%. The transportation sector reported the highest incidence of fatal injuries (35.1/100,000), followed by agriculture (30.5/100,000) and construction (19.3/100,000) sectors. Persons of Indian ethnicity were more likely to sustain fatal injuries compared to other ethnic groups. Conclusions Government and industry should develop rigorous strategies to detect hazards in the workplace, especially in sectors that continuously record high injury rates. Targeted interventions emphasizing worker empowerment coupled with systematic monitoring and evaluation is critical to ensure success in prevention and control measures. PMID:22544443

Estimating fatality rates in occupational light vehicle users using vehicle registration and crash data.

PubMed

Stuckey, Rwth; LaMontagne, Anthony D; Glass, Deborah C; Sim, Malcolm R

2010-04-01

To estimate occupational light vehicle (OLV) fatality numbers using vehicle registration and crash data and compare these with previous estimates based on workers' compensation data. New South Wales (NSW) Roads and Traffic Authority (RTA) vehicle registration and crash data were obtained for 2004. NSW is the only Australian jurisdiction with mandatory work-use registration, which was used as a proxy for work-relatedness. OLV fatality rates based on registration data as the denominator were calculated and comparisons made with published 2003/04 fatalities based on workers' compensation data. Thirty-four NSW RTA OLV-user fatalities were identified, a rate of 4.5 deaths per 100,000 organisationally registered OLV, whereas the Australian Safety and Compensation Council (ASCC), reported 28 OLV deaths Australia-wide. More OLV user fatalities were identified from vehicle registration-based data than those based on workers' compensation estimates and the data are likely to provide an improved estimate of fatalities specific to OLV use. OLV-use is an important cause of traumatic fatalities that would be better identified through the use of vehicle-registration data, which provides a stronger evidence base from which to develop policy responses. © 2010 The Authors. Journal Compilation © 2010 Public Health Association of Australia.

The incidence of drugs in fatally injured drivers

DOT National Transportation Integrated Search

1972-09-01

Method for the collection of blood, urine, bile and alcohol washes of face and fingers from fatally injured drivershave been developed. Specimens have been collected ffom Alcohol Safety ALtion Project areas and other cooperating areas. The samples we...

Human NF-κB1 Haploinsufficiency and Epstein-Barr Virus-Induced Disease-Molecular Mechanisms and Consequences.

PubMed

Hoeger, Birgit; Serwas, Nina Kathrin; Boztug, Kaan

2017-01-01

Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein-Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease.

Case report: Ribavirin and vitamin A in a severe case of measles.

PubMed

Bichon, Amandine; Aubry, Camille; Benarous, Lucas; Drouet, Hortense; Zandotti, Christine; Parola, Philippe; Lagier, Jean-Christophe

2017-12-01

Despite a vaccine being widely available, measles continues to occur frequently, with sometimes lethal consequences. The mortality rate reaches 35% and measles represents 44% of the 1.4 million deaths which are due to preventable diseases. Severe forms of measles are reported, mainly in young, unvaccinated adults, and in specific populations. The risk factors for severe measles include no or incomplete vaccination and vitamin A deficiency. Apart from secondary measles-related infections, severe measles is mainly represented by neurological, respiratory, and digestive symptoms. Strengthening the hypothesis that there is a link between vitamin A deficiency and severe measles in this paper we report the case of a 25-year-old unvaccinated man hospitalized for severe and complicated measles. The evolution was good after administration of intramuscular vitamin A as well as intravenous ribavirin. Measles remains a fatal and serious disease. The early use of ribavirin and vitamin A shows significant improvements regarding morbimortality and should be systematic in severe cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Novel LRPPRC Mutation in a Boy With Mild Leigh Syndrome, French-Canadian Type Outside of Québec.

PubMed

Han, Velda Xinying; Tan, Teresa S; Wang, Furene S; Tay, Stacey Kiat-Hong

2017-01-01

Leigh syndrome, French-Canadian type is unique to patients from a genetic isolate in the Saguenay-Lac-Saint-Jean region of Québec. It has also been recently described in 10 patients with LRPPRC mutation outside of Québec. It is an autosomal recessive genetic disorder with fatal metabolic crisis and severe neurological morbidity in infancy caused by LRPPRC mutation. The authors report a boy with a novel LRPPRC compound heterozygous missense mutations c.3130C>T, c.3430C>T, and c.4078G>A found on whole-exome sequencing which correlated with isolated cytochrome c-oxidase deficiency found in skeletal muscle. LRPPRC mutation is a rare cause of cytochrome c-oxidase-deficient form of Leigh syndrome outside of Québec. Our patient broadens the spectrum of phenotypes of Leigh syndrome, French-Canadian type. LRPPRC mutation should be considered in children with early childhood neurodegenerative disorder, even in the absence of metabolic crisis. Early evaluation with whole-exome sequencing is useful for early diagnosis and for genetic counseling.

Human NF-κB1 Haploinsufficiency and Epstein–Barr Virus-Induced Disease—Molecular Mechanisms and Consequences

PubMed Central

Hoeger, Birgit; Serwas, Nina Kathrin; Boztug, Kaan

2018-01-01

Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein–Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease. PMID:29403474

Loss of β-catenin triggers oxidative stress and impairs hematopoietic regeneration

PubMed Central

Lento, William; Ito, Takahiro; Zhao, Chen; Harris, Jeffrey R.; Huang, Wei; Jiang, Chen; Owzar, Kouros; Piryani, Sadhna; Racioppi, Luigi; Chao, Nelson; Reya, Tannishtha

2014-01-01

Accidental or deliberate ionizing radiation exposure can be fatal due to widespread hematopoietic destruction. However, little is known about either the course of injury or the molecular pathways that regulate the subsequent regenerative response. Here we show that the Wnt signaling pathway is critically important for regeneration after radiation-induced injury. Using Wnt reporter mice, we show that radiation triggers activation of Wnt signaling in hematopoietic stem and progenitor cells. β-Catenin-deficient mice, which lack the ability to activate canonical Wnt signaling, exhibited impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. We found that, as part of the mechanism, hematopoietic stem cells lacking β-catenin fail to suppress the generation of reactive oxygen species and cannot resolve DNA double-strand breaks after radiation. Consistent with the impaired response to radiation, β-catenin-deficient mice are also unable to recover effectively after chemotherapy. Collectively, these data indicate that regenerative responses to distinct hematopoietic injuries share a genetic dependence on β-catenin and raise the possibility that modulation of Wnt signaling may be a path to improving bone marrow recovery after damage. PMID:24788518

Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict.

PubMed

Samstein, Robert M; Josefowicz, Steven Z; Arvey, Aaron; Treuting, Piper M; Rudensky, Alexander Y

2012-07-06

Regulatory T (Treg) cells, whose differentiation and function are controlled by X chromosome-encoded transcription factor Foxp3, are generated in the thymus (tTreg) and extrathymically (peripheral, pTreg), and their deficiency results in fatal autoimmunity. Here, we demonstrate that a Foxp3 enhancer, conserved noncoding sequence 1 (CNS1), essential for pTreg but dispensable for tTreg cell generation, is present only in placental mammals. CNS1 is largely composed of mammalian-wide interspersed repeats (MIR) that have undergone retrotransposition during early mammalian radiation. During pregnancy, pTreg cells specific to a model paternal alloantigen were generated in a CNS1-dependent manner and accumulated in the placenta. Furthermore, when mated with allogeneic, but not syngeneic, males, CNS1-deficient females showed increased fetal resorption accompanied by increased immune cell infiltration and defective remodeling of spiral arteries. Our results suggest that, during evolution, a CNS1-dependent mechanism of extrathymic differentiation of Treg cells emerged in placental animals to enforce maternal-fetal tolerance. Copyright © 2012 Elsevier Inc. All rights reserved.

"What an Affliction": Mary Todd Lincoln's Fatal Pernicious Anemia.

PubMed

Sotos, John G

2015-01-01

To date, no single diagnosis has unified the psychiatric illness and the numerous poorly defined physical complaints that Mary Lincoln (née Todd, 1818-1882) suffered in adulthood. Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment. Long thought hypochondriacal, these findings, plus their time course and her psychopathology (irritability, delusions, hallucinations, with preserved clarity), are all consistent with vitamin B12 deficiency. Pernicious anemia most probably caused this deficiency: she lacked risk factors for other causes, and her consanguineous parents both derived from a region of Scotland having a high incidence of pernicious anemia. A diagnosis of chronic multisystem pernicious anemia would clarify the conduct of Mary Lincoln as First Lady and widow, and illuminate challenges faced by her husband, President Abraham Lincoln. Her case highlights many forgotten features of the natural history of untreated pernicious anemia and is unique in the medical literature in demonstrating such a course extending over a lifetime.

Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.

PubMed

Kido, Masahiro; Watanabe, Norihiko; Okazaki, Taku; Akamatsu, Takuji; Tanaka, Junya; Saga, Kazuyuki; Nishio, Akiyoshi; Honjo, Tasuku; Chiba, Tsutomu

2008-10-01

Because of the lack of animal models developing spontaneous autoimmune hepatitis (AIH), the molecular mechanisms involved in the development of AIH are still unclear. This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH. To induce a concurrent loss of Treg cells and PD-1-mediated signaling, neonatal thymectomy (NTx), which severely reduces the number of Treg cells, was performed on PD-1(-/-) mice. After the NTx, we performed histologic examination, assessed autoantibody production and infiltrating cells in the liver, and conducted adoptive transfer experiments. In contrast to NTx mice and PD-1(-/-) mice, NTx-PD-1(-/-) mice produced antinuclear antibodies and developed fatal hepatitis characterized by a CD4(+) and CD8(+) T-cell infiltration invading the parenchyma with massive lobular necrosis. Induction of AIH in NTx-PD-1(-/-) mice was suppressed by transfer of Treg cells, even derived from PD-1(-/-) mice. Transfer of total but not CD4(+) T-cell-depleted splenocytes from NTx-PD-1(-/-) mice into RAG2(-/-) mice induced the development of severe hepatitis. In contrast, the transfer of CD8(+) T-cell-depleted splenocytes triggered only mononuclear infiltrates without massive necrosis of the parenchyma. NTx-PD-1(-/-) mice are the first mouse model of spontaneous fatal AIH. The concurrent loss of Treg cells and PD-1-mediated signaling can induce the development of fatal AIH. Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage.

Southeast regional fatal study : a causal chain analysis in North Carolina

DOT National Transportation Integrated Search

2002-01-01

This project completed the North Carolina portion of the pooled fund Southeast Fatal Analysis Project. In addition : to completing this portion of the causal chain analysis for NC Crashes, the project developed a ranked : comprehensive list of candid...

Relating traffic fatalities to GDP in Europe on the long term.

PubMed

Antoniou, Constantinos; Yannis, George; Papadimitriou, Eleonora; Lassarre, Sylvain

2016-07-01

Modeling road safety development can provide important insight into policies for the reduction of traffic fatalities. In order to achieve this goal, both the quantifiable impact of specific parameters, as well as the underlying trends that cannot always be measured or observed, need to be considered. One of the key relationships in road safety links fatalities with risk and exposure, where exposure reflects the amount of travel, which in turn translates to how much travelers are exposed to risk. In general two economic variables: GDP and unemployment rate are selected to analyse the statistical relationships with some indicators of road accident fatality risk. The objective of this research is to provide an overview of relevant literature on the topic and outline some recent developments in macro-panel data analysis that have resulted in ongoing research that has the potential to improve our ability to forecast traffic fatality trends, especially under turbulent financial situations. For this analysis, time series of the number of fatalities and GDP in 30 European countries for a period of 38 years (1975-2012) are used. This process relies on estimating long-term models (as captured by long term time-series models, which model each country separately). Based on these developments, utilizing state-of-the-art modelling and analysis techniques such as the Common Correlated Effects Mean Group estimator (Pesaran), the long-term elasticity mean value equals 0.63, and is significantly different from zero for 10 countries only. When we take away the countries, where the number of fatalities is stationary, the average elasticity takes a higher value of nearly 1. This shows the strong sensitivity of the estimate of the average elasticity over a panel of European countries and underlines the necessity to be aware of the underlying nature of the time series, to get a suitable regression model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Defects in maintenance of mitochondrial DNA are associated with intramitochondrial nucleotide imbalances.

PubMed

Ashley, Neil; Adams, Susan; Slama, Abdelhamid; Zeviani, Massimo; Suomalainen, Anu; Andreu, Antonio L; Naviaux, Robert K; Poulton, Joanna

2007-06-15

Defects in mtDNA maintenance range from fatal multisystem childhood diseases, such as Alpers syndrome, to milder diseases in adults, including mtDNA depletion syndromes (MDS) and familial progressive external ophthalmoplegia (AdPEO). Most are associated with defects in genes involved in mitochondrial deoxynucleotide metabolism or utilization, such as mutations in thymidine kinase 2 (TK2) as well as the mtDNA replicative helicase, Twinkle and gamma polymerase (POLG). We have developed an in vitro system to measure incorporation of radiolabelled dNTPs into mitochondria of saponin permeabilized cells. We used this to compare the rates of mtDNA synthesis in cells from 12 patients with diseases of mtDNA maintenance. We observed reduced incorporation of exogenous alpha (32)P-dTTP in fibroblasts from a patient with Alpers syndrome associated with the A467T substitution in POLG, a patient with dGK mutations, and a patient with mtDNA depletion of unknown origin compared to controls. However, incorporation of alpha (32)P-dTTP relative to either cell doubling time or alpha (32)P-dCTP incorporation was increased in patients with thymidine kinase deficiency or PEO as the result of TWINKLE mutations compared with controls. The specific activity of newly synthesized mtDNA depends on the size of the endogenous pool diluting the exogenous labelled nucleotide. Our result is consistent with a deficiency in the intramitochondrial pool of dTTP relative to dCTP in cells from patients with TK2 deficiency and TWINKLE mutations. Such DNA precursor asymmetry could cause pausing of the replication complex and hence exacerbate the propensity for age-related mtDNA mutations. Because deviations from the normal concentrations of dNTPs are known to be mutagenic, we suggest that intramitochondrial nucleotide imbalance could underlie the multiple mtDNA mutations observed in these patients.

The neuropsychiatric profile of Addison's disease: revisiting a forgotten phenomenon.

PubMed

Anglin, Rebecca E; Rosebush, Patricia I; Mazurek, Michael F

2006-01-01

One hundred fifty years since Thomas Addison's original description of the disease, it is not commonly appreciated that patients with Addison's disease may present with psychiatric symptoms. A review of the literature indicates that disturbances in mood, motivation, and behavior are associated with Addison's disease. Psychosis occurs less frequently, but can be the presenting symptom of a life-threatening adrenal crisis. Potential mechanisms for the neuropsychiatric symptoms of Addison's disease include electrophysiological, electrolyte and metabolic abnormalities, glucocorticoid deficiency, increased endorphins, and an associated Hashimoto encephalopathy. Physicians must be aware that Addison's disease may present solely with psychiatric symptoms and maintain a high index of suspicion for this potentially fatal condition.

Cardiac consequences to skeletal muscle-centric therapeutics for Duchenne muscular dystrophy.

PubMed

Townsend, DeWayne; Yasuda, Soichiro; Chamberlain, Jeffrey; Metzger, Joseph M

2009-02-01

Duchenne muscular dystrophy (DMD) is a fatal disease of muscle deterioration. Duchenne muscular dystrophy affects all striated muscles in the body, including the heart. Recent advances in palliative care, largely directed at improving respiratory function, have extended life but paradoxically further unmasked emergent heart disease in DMD patients. New experimental strategies have shown promise in restoring dystrophin in the skeletal muscles of dystrophin- deficient animals. These strategies often have little or no capacity for restitution of dystrophin in the hearts of these animals. This article draws on both clinical data and recent experimental data to posit that effective skeletal muscle restricted therapies for DMD will paradoxically heighten cardiomyopathy and heart failure in these patients.

Occupational fatalities in the United States commercial fishing industry, 2000-2009.

PubMed

Lincoln, Jennifer M; Lucas, Devin L

2010-10-01

The occupational fatality rate among commercial fishermen decreased in the United States during 1992-2008; however, commercial fishing continues to be one of the most dangerous occupations in the United States, with an average annual fatality rate of 129 deaths per 100,000 fishermen in 2008. By contrast, the average annual occupational fatality rate among all US workers during the same period was four deaths per 100,000 workers. During the 1990s, numerous safety interventions were developed for Alaska fisheries that resulted in a significant decline in the state's commercial fishing fatality rate. In 2007, the National Institute for Occupational Safety and Health (NIOSH) expanded surveillance of commercial fishing fatalities to the rest of the United States. The purpose of this report is to identify the hazards and risk factors for all causes of occupational mortality in the US commercial fishing industry, and to explore how those hazards and risk factors differ among fisheries and locations. During 2000-2009, 504 commercial fishing fatalities occurred in the United States. Most (261, 52%) occurred following a vessel disaster (defined as a sinking, capsizing, or other event in which the crew was forced to abandon ship) or a fall overboard (155, 31%). Fatalities occurred in Alaska (133, 26%), Northeast (124, 25%), Gulf of Mexico (116, 23%), West Coast (83, 16%), and the Mid- and South Atlantic (41, 8%) regions. Fatalities occurred most commonly while fishing for shellfish (226, 47%), groundfish (144, 30%) and pelagic fish (97, 20%). Average annual fatality rates were calculated for selected fisheries. The Northeast multispecies groundfish fleet had the highest average annual fatality rate (600 deaths per 100,000 full-time equivalent [FTE] fishermen) followed by the Atlantic scallop fleet (425 deaths per 100,000 FTE fishermen) and the West Coast Dungeness crab fleet (310 deaths per 100,000 FTE fishermen). To reduce fatalities among fishermen at greatest risk, additional prevention measures tailored to specific high-risk fisheries should be considered.

Labor productivity losses over western Turkey in the twenty-first century as a result of alteration in WBGT.

PubMed

Altinsoy, Hamza; Yildirim, Haci Ahmet

2015-04-01

Occupational fatalities and work-related injuries are more common in Turkey than in most developing and developed countries. Several precautions have been taken concerning the matter, and The Occupational Health and Safety Act (OHSL 2012) has been passed. These efforts, however, have failed to incorporate in their framework the role of global warming. New legislation is underway for the prevention of occupational diseases, injuries, and fatalities. This is particularly worrisome given that Turkey is in the forefront of countries projected to be affected seriously by climate change. Consequently, a study on the direct and indirect impact of climate change on workers' health and labour productivity is paramount. The main purpose of this research is to present diminishing labour productivity as a consequence of decreased working hours via an estimate of rest hours of workers in manual labour. The climatic outputs of Regional Climate Model (RegCM3) obtained from the ENSEMBLES Project are used to calculate the wet bulb globe temperature (WBGT) over western Turkey. The study covers the span of years between 1971 and 2100. Moreover, spatial distributions of observed domain are estimated by means of a seasonal analysis, preliminary to a more detailed research. Critical regions, more adversely influenced than others, are identified. The total number of loss days for these critical regions are presented for various time periods. As a result, labour productivity particularly in agriculture and construction is expected to diminish seriously over Central Anatolia, Cyprus, and parts of the Aegean and eastern Mediterranean coastal areas. Between 2071 and 2100, deficiency in labour productivity may reach up to 52% during the summer across some of these critical regions. Though it will be seen that the present study has focused primarily on manual labour and outdoor work in particular, it foreshadows nevertheless the dangerous impact of climate change on occupational health and labour productivity in general.

Labor productivity losses over western Turkey in the twenty-first century as a result of alteration in WBGT

NASA Astrophysics Data System (ADS)

Altinsoy, Hamza; Yildirim, Haci Ahmet

2015-04-01

Occupational fatalities and work-related injuries are more common in Turkey than in most developing and developed countries. Several precautions have been taken concerning the matter, and The Occupational Health and Safety Act (OHSL 2012) has been passed. These efforts, however, have failed to incorporate in their framework the role of global warming. New legislation is underway for the prevention of occupational diseases, injuries, and fatalities. This is particularly worrisome given that Turkey is in the forefront of countries projected to be affected seriously by climate change. Consequently, a study on the direct and indirect impact of climate change on workers' health and labour productivity is paramount. The main purpose of this research is to present diminishing labour productivity as a consequence of decreased working hours via an estimate of rest hours of workers in manual labour. The climatic outputs of Regional Climate Model (RegCM3) obtained from the ENSEMBLES Project are used to calculate the wet bulb globe temperature (WBGT) over western Turkey. The study covers the span of years between 1971 and 2100. Moreover, spatial distributions of observed domain are estimated by means of a seasonal analysis, preliminary to a more detailed research. Critical regions, more adversely influenced than others, are identified. The total number of loss days for these critical regions are presented for various time periods. As a result, labour productivity particularly in agriculture and construction is expected to diminish seriously over Central Anatolia, Cyprus, and parts of the Aegean and eastern Mediterranean coastal areas. Between 2071 and 2100, deficiency in labour productivity may reach up to 52 % during the summer across some of these critical regions. Though it will be seen that the present study has focused primarily on manual labour and outdoor work in particular, it foreshadows nevertheless the dangerous impact of climate change on occupational health and labour productivity in general.

Fatal Liver Cyst Rupture Due to Anabolic Steroid Use: A Case Presentation.

PubMed

Hansma, Patrick; Diaz, Francisco J; Njiwaji, Chantel

2016-03-01

Liver cysts are commonly found incidentally from imaging scans or at autopsy. These benign neoplasms vary in size and represent a heterogeneous group of disorders, for which the demographics, risk factors, apparent inciting event, clinical presentation, and outcome are varied. Complications that can develop from a liver cyst include development of spontaneous hemorrhage, infection, and/or obstruction. Although the etiology of liver cysts varies, fatal rupture of a hemorrhagic liver cyst due to anabolic steroid use is a rare occurrence. In fact, there are few reported cases in journal literature. We report a case of a fatal liver cyst rupture with resultant hemoperitoneum in the presence of anabolic steroid (stanozolol) use.

Fatal injuries caused by logs rolling off trucks: Kentucky 1994-1998.

PubMed

Struttmann, T W; Scheerer, A L

2001-02-01

Logging is one of the most hazardous occupations and fatality rates are consistently among the highest of all industries. A review of fatalities caused by logs rolling off trucks is presented. The Kentucky Fatality Assessment and Control Evaluation Project is a statewide surveillance system for occupational fatalities. Investigations are conducted on selected injuries with an emphasis on prevention strategy development. Logging was an area of high priority for case investigation. During 1994-1998, we identified seven incidents in which a worker was killed by a log rolling off a truck at a sawmill, accounting for 15% of the 45 deaths related to logging activities. These cases were reviewed to identify similar characteristics and risk factors. Investigations led to recommendations for behavioral, administrative, and engineering controls. Potential interventions include limiting load height on trucks, installing unloading cages at sawmills and prohibiting overloaded trucks on public roadways. Copyright 2001 Wiley-Liss, Inc.

Child pedestrian injury and fatality in a developing country.

PubMed

Solagberu, Babatunde Akibu; Osuoji, Roland I; Ibrahim, Nasiru Akanmu; Oludara, Mobolaji A; Balogun, Rufai A; Ajani, Abdulwahab Olanrewaju; Idowu, Olufemi Emmanuel; Mustafa, Ibrahim A; Sanni, Felix O

2014-06-01

Child pedestrian injuries and fatalities in developing countries continue to increase. We examined child pedestrian injuries and fatalities in the most populated urban agglomeration in Africa in order to develop control measures. Two-year prospective study of injured child pedestrians (≤15 years) at the Surgical Emergency Room (SER) to determine demography, vehicles involved, road location, injury mechanism, pre-hospital transport, injury-arrival time, regions injured, injury severity and fatalities was done. Some 226 pedestrians (114 boys and 112 girls) comprising 42 children aged ≤4 years, 91 aged 5-9 years and 93 aged 10-15 years were seen with car collisions (83 pedestrians, 36.7%), motorcycles (76, 33.6%), buses (41, 18.1%), others (15, 6.6%) and 11 undetermined vehicles. Injuries on the highways were 147 (65%); inner-city roads 77 (34.1%) and two undetermined roads. Crossing the road was responsible for 168 (74.3%) pedestrian injuries; while three other mechanisms produced 58 (25.7%) patients. Regions injured were head (42.9%), lower limbs (35.4%) and others (21.7%). Relatives, bystanders and police/ambulance brought 186 (82.3%), 31 (13.7%) and eight (3.5%) children, respectively; and within 6 h (43.4, 11.5 and 2.2%) and after (38.9, 2.2 and 1.3%). Nineteen deaths (10 brought-in-dead, nine SER deaths) occurred; 15 of them girls, 15 had severe head injury, 15 were brought by relatives. However, fatality risks were truck collisions (OR 5.97), female child (OR 4.25), head injury (OR 4.18) and age ≤4 years (OR 3.7). The equal sex incidence, worse female fatality despite similar exposure and injury severity with male, deserve further research. Improved pre-hospital and SER care is needed.

The Characteristics of Road Traffic Fatalities in Kazakhstan’s Semey Region, 2006-2010: A Descriptive Retrospective Study

PubMed Central

MYSSAYEV, Ayan; MEIRMANOV, Serik; RAKHYPBEKOV, Tolebay; BULEGENOV, Tolkyn; SEMENOVA, Yuliya

2014-01-01

Abstract Background Kazakhstan, a developing middle-income country, has the highest road traffic collision (RTC) mortality in the European Region. The aims of this study were to determine main characteristics of road traffic fatalities in Semey region, Kazakhstan and to compare findings with National data and middle-income European countries. Methods This descriptive surveillance study assesses RTC mortality rates and epidemiology in the Semey Region of East Kazakhstan Oblast. Data of all 318 road traffic fatalities form the Semey Regional Center for Forensic Medicine were analyzed for the 5-year period of January 1, 2006 through December 31, 2010. Results Over the study period, the average road traffic mortality in the Semey Region was 12.1 per 100,000 population with downward trend by 35.1% (p=0.002). The victims mean age was 37.1 (SD=17) years. Males predominated at 74.5%. Vehicle fatality was the most common mode of fatality at 61.3%. The majority of collisions, 53.1%, occurred on highways. Most victims, 67.3%, have died at the scene of collision; in 67.3% of fatalities, autopsies identified multiple injuries as cause of death. The high number of fatal collisions took place in “no snow” season (P<0.001), with an overall 5-years downward dynamic. Conclusion High proportion of males, pedestrians and car occupants among road traffic fatalities; high proportion of death on scene in case of highway collisions are specifics for Semey region, Kazakhstan. These findings can be used to formulate preventive strategies to reduce fatalities and to improve the medical care system for road traffic fatalities. PMID:26110146

Factors associated with the severity of fatal accidents in construction workers.

PubMed

Khodabandeh, Farideh; Kabir-Mokamelkhah, Elaheh; Kahani, Mahsa

2016-01-01

Background: Construction work (building houses, roads, workplaces, and repairing and maintaining infrastructures) is a dangerous land-based job. This includes many hazardous tasks and conditions such as working at the following conditions: Height, excavation, noise, dust, power tools and equipment. Construction work has been increased in developed and underdeveloped countries over the past few years. Occupational fatalities have increased with an increase in this type of work. Occupational fatalities refer to individuals who pass way while on the job or performing work related tasks. In the present study, to identify the factors, personal characteristics and work-related factors associated with fatal occupational mortality were assessed using data for Tehran, Iran, 2014-2016. Methods: We conducted a retrospective study, using 967 postmortem reports from fatal occupational injuries collected through postmortem investigations during 2014-2016. A sampling frame of 967 postmortem reports from fatal occupational injuries was used to draw a total sample of 714 fatal construction accidents for this cross-sectional study. Pearson χ2 test and Kruskal-Wallis tests were used for statistical analysis. Results: Based on the results of this study, male gender (n=714; 100%), age range of 30-39 years (n=183; 25.6%), secondary educational level (n=273; 38.2%), being married (317; 44.4%), causal employee (n=389; 54.5%), unskilled performance (389; 54.5%), no insurance coverage (472; 66.1%), and daytime duty work (287; 40.2%) were identified as risk factors for fatality in the event of construction fatal injury. A significant relationship was found between the type of injury and sociodemographic and work related variables. Conclusion: Workers' characteristics such as age, gender, experience, and educational background, and work related variables such as skill training, safety measurement, and close monitoring could be used to discriminate among different severity levels of occupational fatal accidents.

Progress towards zero, an international comparison: Improvements in traffic fatality from 1990 to 2010 for different age groups in the USA and 15 of its peers.

PubMed

Ahangari, Hamed; Atkinson-Palombo, Carol; Garrick, Norman W

2016-06-01

In January 2015, the United States Department of Transportation (USDOT) announced that the official target of the federal government transportation safety policy was zero deaths. Having a better understanding of traffic fatality trends of various age cohorts-and to what extent the US is lagging other countries-is a crucial first step to identifying policies that may help the USDOT achieve its goal. In this paper we analyze fatality rates for different age cohorts in developed countries to better understand how road traffic fatality patterns vary across countries by age cohort. Using benchmarking analysis and comparative index analysis based on panel data modelling and data for selected years between 1990 and 2010, we compare changes in the rate of road traffic fatality over time, as well as the absolute level of road traffic fatality for six age groups in the US, with 15 other developed countries. Our findings illustrate tremendous variations in road fatality rates (both in terms of the absolute values and the rates of improvement over time) among different age cohorts in all of the 16 countries. Looking specifically at the US, our analysis shows that safety improvements for Youngsters (15-17 years old) was much better than for other age groups, and closely tracked peer countries. In sharp contrast, Children (0-14 years old) and Seniors (+65 years old) in the US, fare very poorly when compared to peer countries. For example, in 2010, Children in the US were a stunning five times more likely to experience a road traffic fatality than Children in the UK. This startling statistic suggests an immediate need to explore further the causes and potential solutions to these disparities. This is especially important if countries, including the US, are to achieve the ambitious goals set out in Zero Vision initiatives. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.

Fatal occupational injuries among non-governmental employees in Malaysia.

PubMed

Abas, Adinegara Bin Lutfi; Mohd Said, Datuk Abd Razzak B; Aziz Mohammed, Mohammed Azman B; Sathiakumar, Nalini

2013-01-01

In Malaysia, surveillance of fatal occupational injuries is fragmented. We therefore analyzed an alternative data source from Malaysia's Social Security organization, the Pertubuhan Keselamatan Sosial (PERKESO). We conducted a secondary data analysis of the PERKESO database comprised of 7 million employees from 2002 to 2006. Overall, the average annual incidence was 9.2 fatal occupational injuries per 100,000 workers. During the 5-year period, there was a decrease in the absolute number of fatal injuries by 16% and the incidence by 34%. The transportation sector reported the highest incidence of fatal injuries (35.1/100,000), followed by agriculture (30.5/100,000) and construction (19.3/100,000) sectors. Persons of Indian ethnicity were more likely to sustain fatal injuries compared to other ethnic groups. Government and industry should develop rigorous strategies to detect hazards in the workplace, especially in sectors that continuously record high injury rates. Targeted interventions emphasizing worker empowerment coupled with systematic monitoring and evaluation is critical to ensure success in prevention and control measures. Copyright © 2012 Wiley Periodicals, Inc.

Developing Louisiana crash reduction factors : [tech summary].

DOT National Transportation Integrated Search

2013-10-01

Although, like the rest of the country, Louisiana has made great strides in reducing the number of crashes, particularly : fatal crashes, in recent years, our fatal crash rate of 1.56 is still higher than the national average of 1.10 in 2010. The vis...

Immunization of Knock-Out α/β Interferon Receptor Mice against High Lethal Dose of Crimean-Congo Hemorrhagic Fever Virus with a Cell Culture Based Vaccine

PubMed Central

Canakoglu, Nurettin; Berber, Engin; Tonbak, Sukru; Ertek, Mustafa; Sozdutmaz, Ibrahim; Aktas, Munir; Kalkan, Ahmet; Ozdarendeli, Aykut

2015-01-01

Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne zoonotic disease. The disease has been reported in many countries of Africa, Asia, the Middle East, and in Eurasia. During the past decade, new foci of CCHF have emerged in the Balkan Peninsula, southwest Russia, the Middle East, western China, India, Africa, and Turkey. CCHF virus produces severe hemorrhagic manifestations in humans with fatality rates up to 30%. Vaccine development efforts have been significantly hampered by a lack of animal models and therefore, no protective vaccine has been achieved. Lately, IFN α/β receptor deficient (IFNAR−/−) mice have been established as a novel small animal model of CCHF virus infection. In the present study, we found that IFNAR−/− mice highly susceptible to CCHF virus Turkey-Kelkit06 strain. Immunization with the cell culture based vaccine elicited a significant level of protection against high dose challenge (1,000 PPFU) with a homologous CCHF virus in IFNAR−/− mice. PMID:25760444

A method for estimating the effect of vehicle crashworthiness design changes on injuries and fatalities

DOT National Transportation Integrated Search

1998-02-01

A general methodology is developed for estimating the change in the number of injuries and fatalities expected as a result of a change in vehicle crashworthiness design. It is assumed that crash tests have provided information on dummy response measu...

Alcohol abuse and traffic safety : a study of fatalities, DWI offenders, alcoholics, and court-related treatment approaches

DOT National Transportation Integrated Search

1970-06-26

Author's abstract: Methodology and conclusions on the role of the abusive use of alcohol in traffic safety were developed through three related projects. Project I is a case-history investigation of 616 traffic fatalities from metropolitan Wayne Coun...

A necropsy and histomorphometric study of abnormalities in the course of the vertebral artery associated with ossified stylohyoid ligaments.

PubMed Central

Johnson, C P; Scraggs, M; How, T; Burns, J

1995-01-01

AIMS--To establish whether abnormalities in the course of the vertebral artery occur and whether they are relevant to arterial injury associated with head and neck movements. METHODS--Twenty vertebral arteries were carefully dissected at necropsy and abnormalities in course were noted, along with any other bony or cartilaginous cervical anomalies. The effect of head and neck movement on these vessels was studied before a detailed histomorphometric examination was undertaken on sections of the excised arteries. RESULTS--Five vessels had an abnormal course. One vessel entered the transverse foramina of the fifth cervical vertebra rather than the sixth, but was otherwise normal. In two subjects both vertebral arteries were abnormal in the upper cervical portion with, in each case, a straight left vertebral artery and a right vertebral artery with a deficient loop, closely applied to the atlanto-axial joint. Both of these subjects also had completely ossified stylohyoid ligaments and the arteries visibly stretched with modest head and neck movements. Histology revealed variable degrees of smooth muscle disarray in the tunica media of two of the arteries with loop deficiencies. The circumference of one of the straight arteries was smaller than expected but in all other measured histomorphometric parameters these vessels appeared normal. CONCLUSIONS--Vertebral artery loops are deficient in a number of subjects. This finding is important given the recently described biomechanical susceptibility of the vertebral artery to longitudinal extension and may explain the smooth muscle changes, in that this may represent attempts at arterial wall remodelling. Subjects with such loop deficiencies may be more susceptible to a variety of head and neck insults and such abnormalities should be sought at necropsy in subjects who die as a result of fatal vertebral artery injury. Images PMID:7560170

Fatal mitochondrial encephalopathy caused by fumarase deficiency: A molecular-genetic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gellera, C.; Cavadini, P.; Baratta, S.

Fumarase deficiency is a rare autosomal recessive disorder of the citric acid cycle resulting in severe organic aciduria and encephalopathy. Mammalian cells contain two fumarase isoenzymes, one mitochondrial and one cytosolic. In rat, the two proteins are encoded by the same gene and are synthesized by alternative initiation of translation at two in-phase AUG codons. One single fumarase gene locus has been identified on human chromosome 1. In most of the patients so far described, the activities of both isozymes are severely affected, suggesting that mutations within a single gene may underlie the disease. Here, we report the molecular studymore » of fumarase deficiency in a patient exhibiting compound heterozygosity for two different allelic mutations affecting the amino acid composition of both isoforms. The proband, an Italian boy of nonconsanguineous parents, died at 7 months of age of a progressive encephalopathy. Immunoblot demonstrated absence of cross-reacting material in both cytosolic and mitochondrial fraction of all tissues examined. Molecular analysis of the patient`s fumarase cDNA amplified by RT-PCR showed the presence of two mutations affecting the amino acid composition of both isoforms, a missense mutation resulting in the nonconservative amino acid substitution at codon 190 (Arg190Cys) and an amino acid in-frame insertion at codon 434 (Lys434ins). SSCP analysis of genomic PCR fragments encompassing the mutations demonstrated that the patient was heterozygous for both mutations, having inherited the Arg-to-Cys substitution from the father and the in-frame insertion from the mother. Finally, the effects of the mutations on enzyme function were investigated by expressing both normal and mutated fumarase cDNAs in a fumarase-deficient ({delta}FUM1) S. cerevisiae strain.« less

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency

PubMed Central

Sauer, Aisha Vanessa; Brigida, Immacolata; Carriglio, Nicola; Aiuti, Alessandro

2012-01-01

Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive, and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA), or hematopoietic stem cell gene therapy (HSC-GT). Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment. A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T- and B-cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties. PMID:22969765

Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain Acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency.

PubMed Central

Yokota, I; Coates, P M; Hale, D E; Rinaldo, P; Tanaka, K

1991-01-01

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty-acid oxidation that is characterized by fasting intolerance and recurrent episodes of hypoglycemic coma which can be fatal. Its incidence is one of the highest among genetic metabolic disorders. Using a modified PCR and NcoI digestion method, we have surveyed 46 additional, unrelated MCAD-deficient patients for a prevalent mutation, an 985A-to-G transition (985A----G), that we previously identified in nine MCAD-deficient patients. Among the total of 55 studied, 44 were homozygous and 10 were heterozygous for the 985G allele, whereas one did not carry this mutant allele, indicating that the prevalence of the 985G allele is 89.1%. Furthermore, we identified five other types of mutation: one each in three of the compound heterozygotes and two in the single non-985G patient. An RFLP study of 12 985G-homozygotes showed that all 24 alleles fell into a single haplotype. A questionnaire regarding the ethnic and national origin of their patients was sent to all referring investigators. All 41 patients for whom this information was provided were Caucasians. Of 29 patients whose country of origin was specified, 19 and five were from the British Isles and Germany, respectively. These data suggest that 985A----G may have occurred in a single person in an ancient Germanic tribe. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1684086

Occupational accidents in Russia and the Russian Arctic

PubMed Central

Dudarev, Alexey A.; Karnachev, Igor P.; Odland, Jon Øyvind

2013-01-01

Background According to official statistics, the rate of occupational accidents (OAs) and fatal injuries in Russia decreased about 5-fold and 2-fold, respectively, from 1975 to 2010, but working conditions during this period had the opposite trend; for example, the number of people who work in unfavourable and hazardous conditions (particularly since 1991) has increased significantly. Methods This review summarises the results of a search of the relevant peer-reviewed literature published in Russia and official statistics on OAs and occupational safety in Russia and the Russian Arctic in 1980–2010. Results The occupational safety system in Russia has severely deteriorated in the last 2 decades, with legislators tending to promote the interests of industry and business, resulting in the neglect of occupational safety and violation of workers’ rights. The majority of workers are employed in conditions that do not meet rules of safety and hygiene. More than 60% of OAs can be attributed to management practices – violation of safety regulations, poor organisation of work, deficiency of certified occupational safety specialists and inadequate personnel training. Research aimed at improving occupational safety and health is underfunded. There is evidence of widespread under-reporting of OAs, including fatal accidents. Three federal agencies are responsible for OAs recording; their data differ from each other as they use different methodologies. The rate of fatal OAs in Russia was 3–6 times higher than in Scandinavian countries and about 2 times higher compared to United States and Canada in 2001. In some Russian Arctic regions OAs levels are much higher. Conclusions Urgent improvement of occupational health and safety across Russia, especially in the Arctic regions, is needed. PMID:23519652

Post-transplantation Infections in Bolivia.

PubMed

Arze, S; Arze, L; Abecia, C

2016-03-01

Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic in Bolivia, we had no patients with reactivation or transmission through the graft even though many of the patients and donors were serologically positive for Chagas disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Classification scheme and prevention measures for caught-in-between occupational fatalities.

PubMed

Chi, Chia-Fen; Lin, Syuan-Zih

2018-04-01

The current study analyzed 312 caught-in-between fatalities caused by machinery and vehicles. A comprehensive and mutually exclusive coding scheme was developed to analyze and code each caught-in-between fatality in terms of age, gender, experience of the victim, type of industry, source of injury, and causes for these accidents. Boolean algebra analysis was applied on these 312 caught-in-between fatalities to derive minimal cut set (MCS) causes associated with each source of injury. Eventually, contributing factors and common accident patterns associated with (1) special process machinery including textile, printing, packaging machinery, (2) metal, woodworking, and special material machinery, (3) conveyor, (4) vehicle, (5) crane, (6) construction machinery, and (7) elevator can be divided into three major groups through Boolean algebra and MCS analysis. The MCS causes associated with conveyor share the same primary causes as those of the special process machinery including textile, printing, packaging and metal, woodworking, and special material machinery. These fatalities can be eliminated by focusing on the prevention measures associated with lack of safeguards, working on a running machine or process, unintentional activation, unsafe posture or position, unsafe clothing, and defective safeguards. Other precise and effective intervention can be developed based on the identified groups of accident causes associated with each source of injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of the health impact of occupational risk in Africa: current situation and methodological issues.

PubMed

Loewenson, R

1999-09-01

This paper presents information from the current monitoring systems in Africa, mainly Southern Africa, for occupational illness and injury and discusses the quality of the reported data in estimating the health impact of occupational risk. The paper presents and discusses the current profile of reported injury and fatalities for those countries for which data are available, in particular for the countries of the Southern African Development Community. These data indicate that the reported annual injury rates for wage workers in the Southern African Development Community region range widely from 0.35 to 49.42 injuries per 1,000 workers, and reported occupational fatality in the region ranges from 0.85 to 21.6 fatalities per 100,000 workers. Despite wide variability in reported rates (probably caused by variability in coverage and accuracy of reporting systems), transport, agriculture, mining and, to a lesser extent, construction consistently make up about three-quarters of all fatalities, with vehicle- or transport-related causes accounting for high proportions of fatal accidents. The paper identifies and discusses major sources and direction of bias and error in the reported data and suggests approaches for a better assessment of the health impact of occupational illness, injury, and mortality in African countries.

Estimating direct fatality impacts at wind farms: how far we’ve come, where we have yet to go

USGS Publications Warehouse

Huso, Manuela M.; Schwartz, Susan Savitt

2013-01-01

Measuring the potential impacts of wind farms on wildlife can be difficult and may require development of new statistical tools and models to accurately reflect the measurement process. This presentation reviews the recent history of approaches to estimating wildlife fatality under the unique conditions encountered at wind farms, their unifying themes and their potential shortcomings. Avenues of future research are suggested to continue to address the needs of resource managers and industry in understanding direct impacts of wind turbine-caused wildlife fatality.

Confined space emergency response: assessing employer and fire department practices.

PubMed

Wilson, Michael P; Madison, Heather N; Healy, Stephen B

2012-01-01

An emergency response plan for industrial permit-required confined space entry is essential for employee safety and is legally required. Maintaining a trained confined space rescue team, however, is costly and technically challenging. Some employers turn to public fire departments to meet their emergency response requirements. The confined space emergency response practices of employers and fire departments have not been previously assessed. We present (1) federal data on the U.S. occurrence between 1992 and 2005 of confined space fatal incidents involving toxic and/or oxygen-deficient atmospheres; (2) survey data from 21 large companies on permit-required confined space emergency response practices; (3) data on fire department arrival times; and (4) estimates by 10 senior fire officers of fire department rescue times for confined space incidents. Between 1992 and 2005, 431 confined space incidents that met the case definition claimed 530 lives, or about 0.63% of the 84,446 all-cause U.S. occupational fatal injuries that occurred during this period. Eighty-seven (20%) incidents resulted in multiple fatalities. Twelve (57%) of 21 surveyed companies reported that they relied on the fire department for permit-required confined space emergency response. Median fire department arrival times were about 5 min for engines and 7 min for technical rescue units. Fire department confined space rescue time estimates ranged from 48 to 123 min and increased to 70 and 173 min when hazardous materials were present. The study illustrates that (1) confined space incidents represent a small but continuing source of fatal occupational injuries in the United States; (2) a sizeable portion of employers may be relying on public fire departments for permit-required confined space emergency response; and (3) in the event of a life-threatening emergency, fire departments usually are not able to effect a confined space rescue in a timely manner. We propose that the appropriate role for the fire department is to support a properly trained and equipped on-site rescue team and to provide advanced life support intervention following extrication and during ambulance transportation.

Swarming motility and biofilm formation of Paenibacillus larvae, the etiological agent of American Foulbrood of honey bees (Apis mellifera).

PubMed

Fünfhaus, Anne; Göbel, Josefine; Ebeling, Julia; Knispel, Henriette; Garcia-Gonzalez, Eva; Genersch, Elke

2018-06-11

American Foulbrood is a worldwide distributed, fatal disease of the brood of the Western honey bee (Apis mellifera). The causative agent of this fatal brood disease is the Gram-positive, spore-forming bacterium Paenibacillus larvae, which can be classified into four different genotypes (ERIC I-IV), with ERIC I and II being the ones isolated from contemporary AFB outbreaks. P. larvae is a peritrichously flagellated bacterium and, hence, we hypothesized that P. larvae is capable of coordinated and cooperative multicellular behaviors like swarming motility and biofilm formation. In order to analyze these behaviors of P. larvae, we firstly established appropriate functional assays. Using these assays we demonstrated that P. larvae ERIC II, but not P. larvae ERIC I, was capable of swarming. Swarming motility was hampered in a P. larvae ERIC II-mutant lacking production of paenilarvin, an iturin-like lipopeptide exclusively expressed by this genotype. Both genotypes were able to form free floating biofilm aggregates loosely attached to the walls of the culture wells. Visualizing the biofilms by Congo red and thioflavin S staining suggested structural differences between the biofilms formed. Biofilm formation was shown to be independent from paenilarvin production because the paenilarvin deficient mutant was comparably able to form a biofilm.

Intervention strategies to eliminate truck-related fatalities in surface coal mining in West Virginia.

PubMed

Zhang, Meng; Kecojevic, Vladislav

2016-01-01

The main objective of this review was to build upon a previous study on the root causes of truck-related fatalities in surface coal mining operations in West Virginia, and to develop intervention strategies to eliminate these fatalities. This review considers a two-pronged approach to accident prevention: one that is fundamental and traditional (safety regulations, training and education, and engineering of the work environment); and one that is innovative and creative (e.g., applying technological advances to better control and eliminate the root causes of accidents). Suggestions for improving current training and education system are proposed, and recommendations are provided on improving the safety of mine working conditions, specifically safety conditions on haul roads, dump sites, and loading areas. We also discuss various currently available technologies that can help prevent haul truck-related fatal accidents. The results of this review should be used by mine personnel to help create safer working conditions and decrease truck-related fatalities in surface coal mining.

Investigation of shipping accident injury severity and mortality.

PubMed

Weng, Jinxian; Yang, Dong

2015-03-01

Shipping movements are operated in a complex and high-risk environment. Fatal shipping accidents are the nightmares of seafarers. With ten years' worldwide ship accident data, this study develops a binary logistic regression model and a zero-truncated binomial regression model to predict the probability of fatal shipping accidents and corresponding mortalities. The model results show that both the probability of fatal accidents and mortalities are greater for collision, fire/explosion, contact, grounding, sinking accidents occurred in adverse weather conditions and darkness conditions. Sinking has the largest effects on the increment of fatal accident probability and mortalities. The results also show that the bigger number of mortalities is associated with shipping accidents occurred far away from the coastal area/harbor/port. In addition, cruise ships are found to have more mortalities than non-cruise ships. The results of this study are beneficial for policy-makers in proposing efficient strategies to prevent fatal shipping accidents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Wernicke-Korsakoff syndrome: recognition and treatment.

PubMed

Donnelly, Alexander

2017-03-29

Wernicke-Korsakoff syndrome is a potentially debilitating and fatal condition that is caused by thiamine (vitamin B1) deficiency in the brain. It can be treated effectively or prevented completely; however, the condition is often undiagnosed and inadequately managed. Wernicke-Korsakoff syndrome is commonly considered to be specific to individuals who misuse alcohol; however, there are many other predisposing factors and causes associated with the condition. This article aims to raise awareness of Wernicke-Korsakoff syndrome, to enable nurses in all practice settings to recognise the signs, symptoms and risk factors associated with the condition and be informed about available treatments. Increased awareness aims to improve early diagnosis of the condition, enabling effective treatment and improving patients' symptoms, such as cognitive impairment.

Reducing the legal blood alcohol concentration limit for driving in developing countries: a time for change? Results and implications derived from a time-series analysis (2001-10) conducted in Brazil.

PubMed

Andreuccetti, Gabriel; Carvalho, Heraclito B; Cherpitel, Cheryl J; Ye, Yu; Ponce, Julio C; Kahn, Tulio; Leyton, Vilma

2011-12-01

In Brazil, a new law introduced in 2008 has lowered the blood alcohol concentration limit for drivers from 0.06 to 0.02, but the effectiveness in reducing traffic accidents remains uncertain. This study evaluated the effects of this enactment on road traffic injuries and fatalities. Time-series analysis using autoregressive integrated moving average (ARIMA) modelling. State and capital of São Paulo, Brazil.   A total of 1,471,087 non-fatal and 51,561 fatal road traffic accident cases in both regions. Monthly rates of traffic injuries and fatalities per 100,000 inhabitants from January 2001 to June 2010. The new traffic law was responsible for significant reductions in traffic injury and fatality rates in both localities (P<0.05). A stronger effect was observed for traffic fatality (-7.2 and -16.0% in the average monthly rate in the State and capital, respectively) compared to traffic injury rates (-1.8 and -2.3% in the State and capital, respectively). Lowering the blood alcohol concentration limit in Brazil had a greater impact on traffic fatalities than injuries, with a higher effect in the capital, where presumably the police enforcement was enhanced. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Graduated licensing laws and fatal crashes of teenage drivers: a national study.

PubMed

McCartt, Anne T; Teoh, Eric R; Fields, Michele; Braitman, Keli A; Hellinga, Laurie A

2010-06-01

The objective of the current study was to quantify the effects of the strength of US state graduated driver licensing laws and specific licensing components on the rate of teenage driver fatal crash involvements per 100,000 teenagers during 1996-2007. The strengths of state laws were rated good, fair, marginal, or poor based on a system developed previously by the Insurance Institute for Highway Safety. Analysis was based on quarterly counts of drivers involved in fatal crashes. Associations of overall ratings and individual licensing components with teenage crash rates were evaluated using Poisson regression, with the corresponding fatal crash rate for drivers ages 30-59 controlling for state- or time-dependent influences on crash rates unrelated to graduated licensing laws. Compared with licensing laws rated poor, laws rated good were associated with 30 percent lower fatal crash rates among 15- to 17-year-olds. Laws rated fair yielded fatal crash rates 11 percent lower. The longer the permit age was delayed, or the longer the licensing age was delayed, the lower the estimated fatal crash rates among 15- to 17-year-olds. Stronger nighttime restrictions were associated with larger reductions, and reductions were larger for laws limiting teenage passengers to zero or one than laws allowing two or more teenage passengers or laws without passenger restrictions. After the effects of any related delay in licensure were accounted for, an increase in the minimum learner's permit holding period showed no association with fatal crash rates. An increase in required practice driving hours did not appear to have an independent association with fatal crash rates. Graduated licensing laws that include strong nighttime and passenger restrictions and laws that delay the learner's permit age and licensing age are associated with lower teenage fatal crash rates. States that adopt such laws can expect to achieve substantial reductions in crash deaths.

Factors associated with the severity of fatal accidents in construction workers

PubMed Central

Khodabandeh, Farideh; Kabir-Mokamelkhah, Elaheh; Kahani, Mahsa

2016-01-01

Background: Construction work (building houses, roads, workplaces, and repairing and maintaining infrastructures) is a dangerous land-based job. This includes many hazardous tasks and conditions such as working at the following conditions: Height, excavation, noise, dust, power tools and equipment. Construction work has been increased in developed and underdeveloped countries over the past few years. Occupational fatalities have increased with an increase in this type of work. Occupational fatalities refer to individuals who pass way while on the job or performing work related tasks. In the present study, to identify the factors, personal characteristics and work-related factors associated with fatal occupational mortality were assessed using data for Tehran, Iran, 2014-2016. Methods: We conducted a retrospective study, using 967 postmortem reports from fatal occupational injuries collected through postmortem investigations during 2014-2016. A sampling frame of 967 postmortem reports from fatal occupational injuries was used to draw a total sample of 714 fatal construction accidents for this cross-sectional study. Pearson χ2 test and Kruskal-Wallis tests were used for statistical analysis. Results: Based on the results of this study, male gender (n=714; 100%), age range of 30-39 years (n=183; 25.6%), secondary educational level (n=273; 38.2%), being married (317; 44.4%), causal employee (n=389; 54.5%), unskilled performance (389; 54.5%), no insurance coverage (472; 66.1%), and daytime duty work (287; 40.2%) were identified as risk factors for fatality in the event of construction fatal injury. A significant relationship was found between the type of injury and sociodemographic and work related variables. Conclusion: Workers’ characteristics such as age, gender, experience, and educational background, and work related variables such as skill training, safety measurement, and close monitoring could be used to discriminate among different severity levels of occupational fatal accidents. PMID:28491844

Intra-operative hyperthermia in a young Angus bull with a fatal outcome.

PubMed

Skelding, Alicia; Valverde, Alexander

2017-06-01

A healthy, 9-month-old black Angus bull was presented for elective penile-preputial translocation and caudal epididymectomy. After premedication and induction, general anesthesia was maintained with inhalant anesthetic. Over an hour into the anesthetic period the bull developed severe hyperthermia and hypercapnia that resulted in fatality despite treatment efforts.

Calibration of the Highway Safety Manual and development of new safety performance functions for rural multilane highways in Kansas : technical summary.

DOT National Transportation Integrated Search

2016-10-01

Rural roads account for 90.3% of the 140,476 total centerline miles of roadways : in Kansas. In recent years, rural fatal crashes have accounted for about 66% : of all fatal crashes. The Highway Safety Manual (HSM) provides models and : methodologies...

Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting.

PubMed

Molyneux, Elizabeth; Ahmad, Shafique; Robertson, Ann

2006-04-01

Early assessment, prioritization for treatment and management of sick children attending a health service are critical to achieving good outcomes. Many hospitals in developing countries see large numbers of patients and have few staff, so patients often have to wait before being assessed and treated. We present the example of a busy Under-Fives Clinic that provided outpatient services, immunizations and treatment for medical emergencies. The clinic was providing an inadequate service resulting in some inappropriate admissions and a high case-fatality rate. We assessed the deficiencies and sought resources to improve services. A busy paediatric outpatient clinic in a public tertiary care hospital in Blantyre, Malawi. The main changes we made were to train staff in emergency care and triage, improve patient flow through the department and to develop close cooperation between inpatient and outpatient services. Training coincided with a restructuring of the physical layout of the department. The changes were put in place when the department reopened in January 2001. Improvements in the process and delivery of care and the ability to prioritize clinical management are essential to good practice. Making the changes described above has streamlined the delivery of care and led to a reduction in inpatient mortality from 10-18% before the changes were made (before 2001) to 6-8% after.

Comparison of enrofloxacin and ceftiofur sodium for the treatment of relapse of undifferentiated fever/bovine respiratory disease in feedlot cattle.

PubMed

Abutarbush, Sameeh M; Schunicht, Oliver C; Wildman, Brian K; Hannon, Sherry J; Jim, G Kee; Ward, Tracy I; Booker, Calvin W

2012-01-01

This commercial field trial compared the efficacy of enrofloxacin and ceftiofur sodium in beef cattle at high risk of developing undifferentiated fever (UF), also known as bovine respiratory disease (BRD) that received tilmicosin at feedlot arrival, were diagnosed and initially treated for UF with tilmicosin, and subsequently required a second UF treatment (first relapse). Feedlot cattle (n = 463) were randomly assigned to 2 experimental groups: ENRO or CEF. Second UF relapse, 3rd UF relapse, overall case fatality and BRD case fatality rates were lower in the ENRO group than in the CEF group (P < 0.05). There were no differences in average daily gain (allocation to re-implant date), chronicity, histophilosis case fatality or miscellaneous case fatality rates between the groups (P ≥ 0.05). A per-animal economic advantage of Can$57.08 was calculated for the ENRO group versus the CEF group. In feedlot cattle in western Canada at high risk of developing UF, it was more cost effective to administer enrofloxacin than ceftiofur sodium for treatment of UF relapse.

Comparison of enrofloxacin and ceftiofur sodium for the treatment of relapse of undifferentiated fever/bovine respiratory disease in feedlot cattle

PubMed Central

Abutarbush, Sameeh M.; Schunicht, Oliver C.; Wildman, Brian K.; Hannon, Sherry J.; Jim, G. Kee; Ward, Tracy I.; Booker, Calvin W.

2012-01-01

This commercial field trial compared the efficacy of enrofloxacin and ceftiofur sodium in beef cattle at high risk of developing undifferentiated fever (UF), also known as bovine respiratory disease (BRD) that received tilmicosin at feedlot arrival, were diagnosed and initially treated for UF with tilmicosin, and subsequently required a second UF treatment (first relapse). Feedlot cattle (n = 463) were randomly assigned to 2 experimental groups: ENRO or CEF. Second UF relapse, 3rd UF relapse, overall case fatality and BRD case fatality rates were lower in the ENRO group than in the CEF group (P < 0.05). There were no differences in average daily gain (allocation to re-implant date), chronicity, histophilosis case fatality or miscellaneous case fatality rates between the groups (P ≥ 0.05). A per-animal economic advantage of Can$57.08 was calculated for the ENRO group versus the CEF group. In feedlot cattle in western Canada at high risk of developing UF, it was more cost effective to administer enrofloxacin than ceftiofur sodium for treatment of UF relapse. PMID:22753964

Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options

PubMed Central

Yadak, Rana; Sillevis Smitt, Peter; van Gisbergen, Marike W.; van Til, Niek P.; de Coo, Irenaeus F. M.

2017-01-01

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency. The lack of TP results in systemic accumulation of deoxyribonucleosides thymidine (dThd) and deoxyuridine (dUrd). In these patients, clinical features include mental regression, ophthalmoplegia, and fatal gastrointestinal complications. The accumulation of nucleosides also causes imbalances in mitochondrial DNA (mtDNA) deoxyribonucleoside triphosphates (dNTPs), which may play a direct or indirect role in the mtDNA depletion/deletion abnormalities, although the exact underlying mechanism remains unknown. The available therapeutic approaches include dialysis and enzyme replacement therapy, both can only transiently reverse the biochemical imbalance. Allogeneic hematopoietic stem cell transplantation is shown to be able to restore normal enzyme activity and improve clinical manifestations in MNGIE patients. However, transplant related complications and disease progression result in a high mortality rate. New therapeutic approaches, such as adeno-associated viral vector and hematopoietic stem cell gene therapy have been tested in Tymp-/-Upp1-/- mice, a murine model for MNGIE. This review provides background information on disease manifestations of MNGIE with a focus on current management and treatment options. It also outlines the pre-clinical approaches toward future treatment of the disease. PMID:28261062

Switch from type II to I Fas/CD95 death signaling upon in vitro culturing of primary hepatocytes

PubMed Central

Walter, Dorothée; Schmich, Kathrin; Vogel, Sandra; Pick, Robert; Kaufmann, Thomas; Hochmuth, Florian Christoph; Haber, Angelika; Neubert, Karin; McNelly, Sabine; von Weizsäcker, Fritz; Merfort, Irmgard; Maurer, Ulrich; Strasser, Andreas; Borner, Christoph

2010-01-01

Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the pro-apoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. Here we report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel™, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, FasL activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from TNFα/ActD-induced apoptosis. Conclusion Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling which favours mitochondria-independent type I apoptosis induction. PMID:19003879

Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).

PubMed

Booth, Claire; Gaspar, H Bobby

2009-01-01

Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes.

PubMed

Walter, Dorothée; Schmich, Kathrin; Vogel, Sandra; Pick, Robert; Kaufmann, Thomas; Hochmuth, Florian Christoph; Haber, Angelika; Neubert, Karin; McNelly, Sabine; von Weizsäcker, Fritz; Merfort, Irmgard; Maurer, Ulrich; Strasser, Andreas; Borner, Christoph

2008-12-01

Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the proapoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. We report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, Fas ligand (FasL) activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from tumor necrosis factor alpha/actinomycin D (TNFalpha/ActD)-induced apoptosis. Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling that favors mitochondria-independent type I apoptosis induction.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model.

PubMed

Beaver, Laura M; Nkrumah-Elie, Yasmeen M; Truong, Lisa; Barton, Carrie L; Knecht, Andrea L; Gonnerman, Greg D; Wong, Carmen P; Tanguay, Robert L; Ho, Emily

2017-05-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring's mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. Published by Elsevier Inc.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model

PubMed Central

Beaver, Laura M.; Nkrumah-Elie, Yasmeen M.; Truong, Lisa; Barton, Carrie L.; Knecht, Andrea L.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

2017-01-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring’s mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. PMID:28268202

Asian and Hispanic Americans' cancer fatalism and colon cancer screening.

PubMed

Jun, Jungmi; Oh, Kyeung Mi

2013-03-01

To explore fatalistic attributions of colon cancer development among Asian and Hispanic Americans in comparison with non-Hispanic whites; also to examine the impacts of fatalism on adherence to the colon cancer screening guideline. For the analysis, the 2005 Health Information National Trends Survey data were employed. Both Asian and Hispanic Americans were more likely to make fatalistic attribution and were less likely to follow the guideline than whites. Particularly for Asians, fatalism was a significant predictor for not adhering to the guideline. These findings emphasize the need for cultural interventions to disrupt fatalistic attitudes towards colon cancer preventions.

Characteristics of non-fatal self-poisoning in Sri Lanka: a systematic review

PubMed Central

2013-01-01

Background The rate of non-fatal self-poisoning in Sri Lanka has increased in recent years, with associated morbidity and economic cost to the country. This review examines the published literature for the characteristics and factors associated with non-fatal self-poisoning in Sri Lanka. Methods Electronic searches were conducted in Psychinfo, Proquest, Medline and Cochrane databases from inception to October 2011. Results 26 publications (representing 23 studies) were eligible to be included in the review. A majority of studies reported non-fatal self-poisoning to be more common among males, with a peak age range of 10–30 years. Pesticide ingestion was the most commonly used method of non-fatal self-poisoning. However three studies conducted within the last ten years, in urban areas of the country, reported non-fatal self-poisoning by medicinal overdose to be more common, and also reported non-fatal self-poisoning to be more common among females. Interpersonal conflict was the most commonly reported short-term stressor associated with self-poisoning. Alcohol misuse was reported among males who self-poisoned, and data regarding other psychiatric morbidity was limited. Conclusions The findings indicate that pesticide ingestion is the commonest method of non-fatal self-poisoning in Sri Lanka, and it is more common among young males, similar to other Asian countries. However there appears to be an emerging pattern of increasing medicinal overdoses, paralleled by a gender shift towards increased female non-fatal self-poisoning in urban areas. Many non-fatal self-poisoning attempts appear to occur in the context of acute interpersonal stress, with short premeditation, and associated with alcohol misuse in males. Similar to other Asian countries, strategies to reduce non-fatal self-poisoning in Sri Lanka require integrated intervention programs with several key aspects, including culturally appropriate interventions to develop interpersonal skills in young people, community based programs to reduce alcohol misuse, and screening for and specific management of those at high risk of repetition following an attempt of self-poisoning. PMID:23575389

Are We Ready for Mass Fatality Incidents? Preparedness of the US Mass Fatality Infrastructure.

PubMed

Merrill, Jacqueline A; Orr, Mark; Chen, Daniel Y; Zhi, Qi; Gershon, Robyn R

2016-02-01

To assess the preparedness of the US mass fatality infrastructure, we developed and tested metrics for 3 components of preparedness: organizational, operational, and resource sharing networks. In 2014, data were collected from 5 response sectors: medical examiners and coroners, the death care industry, health departments, faith-based organizations, and offices of emergency management. Scores were calculated within and across sectors and a weighted score was developed for the infrastructure. A total of 879 respondents reported highly variable organizational capabilities: 15% had responded to a mass fatality incident (MFI); 42% reported staff trained for an MFI, but only 27% for an MFI involving hazardous contaminants. Respondents estimated that 75% of their staff would be willing and able to respond, but only 53% if contaminants were involved. Most perceived their organization as somewhat prepared, but 13% indicated "not at all." Operational capability scores ranged from 33% (death care industry) to 77% (offices of emergency management). Network capability analysis found that only 42% of possible reciprocal relationships between resource-sharing partners were present. The cross-sector composite score was 51%; that is, half the key capabilities for preparedness were in place. The sectors in the US mass fatality infrastructure report suboptimal capability to respond. National leadership is needed to ensure sector-specific and infrastructure-wide preparedness for a large-scale MFI.

Non-fatal self-poisoning in Sri Lanka: associated triggers and motivations.

PubMed

Rajapakse, Thilini; Griffiths, Kathleen Margaret; Christensen, Helen; Cotton, Sue

2015-11-24

Attempted or non-fatal self-poisoning is common in Sri Lanka. To date, most preventive strategies have focused on limitation of access to toxic pesticides, which has reduced the rates of fatal self-poisoning. However the ongoing phenomenon of non-fatal self-poisoning indicates the need for exploration of alternate preventive strategies. Self-poisoning in Sri Lanka has been described as impulsive, with little premeditation, but the motivations associated with this act have not been studied in depth. This research describes the triggers and motivations associated with non-fatal self-poisoning in Sri Lanka. It is anticipated that the findings would help guide future preventive strategies. Two studies were carried out, at Teaching Hospital Peradeniya, Sri Lanka, each using a different methodology - Study 1 consisted of qualitative semi-structured interviews, and Study 2 was a cross sectional survey. Both studies were conducted among those who had recently attempted self-poisoning, and explored associated triggers and motivations associated with the act of self-poisoning. There was no overlap between participants of the two studies. A total of 24 persons participated in the semi-structured interviews (Study 1), and 921 took part in the cross-sectional survey (Study 2). Interpersonal conflict was the most common trigger prior to the act of non-fatal self-poisoning. A mixture of motivations was associated with the act of self-poisoning, including intent to die, to escape, and difficulty tolerating distress associated with interpersonal conflict. Development of interpersonal skills and interpersonal problem solving skills, particularly in adolescents and young people, emerges as a key primary preventive strategy. Further, there is value in exploring and helping people to develop more adaptive strategies to cope with emotional distress associated with interpersonal conflict. While distress tolerance and interpersonal skill training strategies used in the West may be considered, it is also important to adapt and develop strategies suited to the local cultural background. Further research is needed to develop and evaluate such strategies, and findings may have implications not only to Sri Lanka but also for other countries in South Asia.

Calibration of the highway safety manual and development of new safety performance functions for rural multilane highways in Kansas : final report.

DOT National Transportation Integrated Search

2016-10-01

Rural roads account for 90.3% of the 140,476 total centerline miles of roadways in Kansas. In recent years, rural fatal crashes have accounted for about 66% of all fatal crashes. The Highway Safety Manual (HSM) provides models and methodologies for a...

Fatal dissecting aneurysm of the aorta in a diver.

PubMed

James, R; Hayman, J A

1986-07-01

A 20-yr-old trained sports diver developed severe chest pain shortly after decompressing from a 40 m repetitive freshwater sinkhole dive, and died 6 h later. An autopsy examination showed a dissecting aneurysm of the aorta with rupture into the left pleural cavity. The relationship between the fatal event and the diving is discussed.

Unusual Severe Complication Following Transarterial Chemoembolization for Metastatic Malignant Melanoma: Giant Intrahepatic Cyst and Fatal Hepatic Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ataergin, Selmin, E-mail: sataergin@superonline.co; Tasar, Mustafa; Solchaga, Luis

2009-03-15

We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

Overview of the NASA Systems Approach to Crashworthiness Program

NASA Technical Reports Server (NTRS)

Jones, Lisa E.

2002-01-01

The NASA Aviation Safety Program was developed in response to the federal government's goal to reduce the fatal accident rate for aviation by 80% within 10 years. Accident Mitigation is a primary element of the Aviation Safety Program. The overall Accident Mitigation goal is to provide technology to the air transport industry to enable a decrease in the rate of fatalities and injury from crash loads and from in-flight and post-crash explosion and/or fire. Accident Mitigation is divided into two main elements - Fire Prevention and Systems Approach to Crashworthiness. The Systems Approach to Crashworthiness goal is to develop and promote technology that will increase the human survival rate or reduce the fatality rate in survivable accidents. The technical background and planning, selected technical activities, and summary of future efforts will be presented in this paper.

Chlorine truck attack consequences and mitigation.

PubMed

Barrett, Anthony Michael; Adams, Peter J

2011-08-01

We develop and apply an integrated modeling system to estimate fatalities from intentional release of 17 tons of chlorine from a tank truck in a generic urban area. A public response model specifies locations and actions of the populace. A chemical source term model predicts initial characteristics of the chlorine vapor and aerosol cloud. An atmospheric dispersion model predicts cloud spreading and movement. A building air exchange model simulates movement of chlorine from outdoors into buildings at each location. A dose-response model translates chlorine exposures into predicted fatalities. Important parameters outside defender control include wind speed, atmospheric stability class, amount of chlorine released, and dose-response model parameters. Without fast and effective defense response, with 2.5 m/sec wind and stability class F, we estimate approximately 4,000 (half within ∼10 minutes) to 30,000 fatalities (half within ∼20 minutes), depending on dose-response model. Although we assume 7% of the population was outdoors, they represent 60-90% of fatalities. Changing weather conditions result in approximately 50-90% lower total fatalities. Measures such as sheltering in place, evacuation, and use of security barriers and cryogenic storage can reduce fatalities, sometimes by 50% or more, depending on response speed and other factors. © 2011 Society for Risk Analysis.

Anorexia nervosa and Wernicke-Korsakoff syndrome: a case report

PubMed Central

2010-01-01

Introduction Wernicke's encephalopathy is an acute, potentially fatal, neuropsychiatric syndrome resulting from thiamine deficiency. The disorder is still greatly under-diagnosed, and failure to promptly identify and adequately treat the condition can lead to death or to the chronic form of the encephalopathy - Korsakoff's syndrome. Wernicke's encephalopathy has traditionally been associated with alcoholism but, in recent years, there has been an increase in the number of clinical settings in which the disorder is observed. Case presentation We report the case of a 45-year-old Caucasian woman who arrived at the emergency room presenting signs of marked malnutrition and mental confusion, ataxic gait and ophthalmoplegia. Main laboratory test findings included low serum magnesium and megaloblastic anemia. Brain magnetic resonance imaging revealed increased T2 signal in the supratentorial paraventricular region, the medial regions of the thalamus and the central and periaqueductal midbrain. The diagnosis of Wernicke's encephalopathy was made at once and immediate reposition of thiamine and magnesium was started. The patient had a long history of recurrent thoughts of being overweight, severe self-imposed diet restrictions and self-induced vomiting. She had also been drinking gin on a daily basis for the last eight years. One day after admittance the acute global confusional state resolved, but she presented severe memory deficits and confabulation. After six months of outpatient follow-up, memory deficits remained unaltered. Conclusion In this case, self-imposed long-lasting nutritional deprivation is thought to be the main cause of thiamine deficiency and subsequent encephalopathy, but adjunct factors, such as magnesium depletion and chronic alcohol misuse, might have played an important role, especially in the development of Korsakoff's syndrome. The co-morbidity between eating disorders and substance abuse disorders has emerged as a significant health issue for women, and the subgroup of patients with anorexia nervosa who also misuse alcohol is probably at a particular risk of developing Wernicke-Korsakoff syndrome. The present case report highlights this relevant issue. PMID:20646296

Anorexia nervosa and Wernicke-Korsakoff syndrome: a case report.

PubMed

Saad, Laura; Silva, Luiz Fal; Banzato, Claudio Em; Dantas, Clarissa R; Garcia, Celso

2010-07-20

Wernicke's encephalopathy is an acute, potentially fatal, neuropsychiatric syndrome resulting from thiamine deficiency. The disorder is still greatly under-diagnosed, and failure to promptly identify and adequately treat the condition can lead to death or to the chronic form of the encephalopathy - Korsakoff's syndrome. Wernicke's encephalopathy has traditionally been associated with alcoholism but, in recent years, there has been an increase in the number of clinical settings in which the disorder is observed. We report the case of a 45-year-old Caucasian woman who arrived at the emergency room presenting signs of marked malnutrition and mental confusion, ataxic gait and ophthalmoplegia. Main laboratory test findings included low serum magnesium and megaloblastic anemia. Brain magnetic resonance imaging revealed increased T2 signal in the supratentorial paraventricular region, the medial regions of the thalamus and the central and periaqueductal midbrain. The diagnosis of Wernicke's encephalopathy was made at once and immediate reposition of thiamine and magnesium was started. The patient had a long history of recurrent thoughts of being overweight, severe self-imposed diet restrictions and self-induced vomiting. She had also been drinking gin on a daily basis for the last eight years. One day after admittance the acute global confusional state resolved, but she presented severe memory deficits and confabulation. After six months of outpatient follow-up, memory deficits remained unaltered. In this case, self-imposed long-lasting nutritional deprivation is thought to be the main cause of thiamine deficiency and subsequent encephalopathy, but adjunct factors, such as magnesium depletion and chronic alcohol misuse, might have played an important role, especially in the development of Korsakoff's syndrome. The co-morbidity between eating disorders and substance abuse disorders has emerged as a significant health issue for women, and the subgroup of patients with anorexia nervosa who also misuse alcohol is probably at a particular risk of developing Wernicke-Korsakoff syndrome. The present case report highlights this relevant issue.

Fatal and nonfatal risk associated with recycle of D&D-generated concrete

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boren, J.K.; Ayers, K.W.; Parker, F.L.

1997-02-01

As decontamination and decommissioning activities proceed within the U.S. Department of Energy Complex, vast volumes of uncontaminated and contaminated concrete will be generated. The current practice of decontaminating and landfilling the concrete is an expensive and potentially wasteful practice. Research is being conducted at Vanderbilt University to assess the economic, social, legal, and political ramifications of alternate methods of dealing with waste concrete. An important aspect of this research work is the assessment of risk associated with the various alternatives. A deterministic risk assessment model has been developed which quantifies radiological as well as non-radiological risks associated with concrete disposalmore » and recycle activities. The risk model accounts for fatal as well as non-fatal risks to both workers and the public. Preliminary results indicate that recycling of concrete presents potentially lower risks than the current practice. Radiological considerations are shown to be of minor importance in comparison to other sources of risk, with conventional transportation fatalities and injuries dominating. Onsite activities can also be a major contributor to non-fatal risk.« less

Alcohol Policies and Alcohol-Related Motor Vehicle Crash Fatalities Among Young People in the US.

PubMed

Hadland, Scott E; Xuan, Ziming; Sarda, Vishnudas; Blanchette, Jason; Swahn, Monica H; Heeren, Timothy C; Voas, Robert B; Naimi, Timothy S

2017-03-01

Motor vehicle crashes (MVCs) are a leading cause of death among young people in the United States. We examined the relationship between states' alcohol policy environments and alcohol-related MVC fatalities among children, adolescents, and young adults under the minimum legal drinking age of 21 years. We used the Alcohol Policy Scale (APS), an assessment of 29 alcohol policies across 50 states and Washington, DC, developed with the assistance of an interdisciplinary Delphi panel. Using the Fatality Analysis Reporting System, we examined APS scores in relation to fatalities of people ≤20 years old from 2000 to 2013 occurring in crashes in which ≥1 involved driver had a blood alcohol content ≥0.08%. Logistic regression was used with a 1-year lag between policies and MVC fatalities and adjusted for potential confounders. Of 84 756 MVC fatalities of those ≤20 years old during the study period, 23 757 (28.0%) were alcohol related, including deaths of 11 006 (46.3%) drivers, 10 212 (43.0%) passengers, and 2539 (10.7%) pedestrians, cyclists, and others. People killed in alcohol-related MVCs were predominantly male (72.7%) and older (65.5% were 18-20 years old), and 51.2% were non-Hispanic white. Restrictive policy environments were associated with fewer fatalities (adjusted odds ratio, 0.91 per 10-percentage-point increase in APS score; 95% confidence interval, 0.89-0.94). The association was observed for drivers and passengers, male and female decendents, and children, adolescents, and young adults. More restrictive alcohol policies are associated with reduced alcohol-related MVC mortality among young people. Studies should scrutinize the relationship between policies and fatalities to highlight mechanisms. Copyright © 2017 by the American Academy of Pediatrics.

Disease fatality and bias in survival cohorts.

PubMed

Barry, Vaughn; Klein, Mitchel; Winquist, Andrea; Darrow, Lyndsey A; Steenland, Kyle

2015-07-01

Simulate how the effect of exposure on disease occurrence and fatality influences the presence and magnitude of bias in survivor cohorts, motivated by an actual survivor cohort under study. We simulated a cohort of 50,000 subjects exposed to a disease-causing exposure over time and followed forty years, where disease incidence was the outcome of interest. We simulated this 'inception' cohort under different assumptions about the effect of exposure on disease occurrence and fatality after disease occurrence. We then created a corresponding 'survivor' (or 'cross-sectional') cohort, where cohort enrollment took place at a specific date after exposure began in the inception cohort; subjects dying prior to that enrollment date were excluded. The disease of interest caused all deaths in our simulations, but was not always fatal. In the survivor cohort, person-time at risk began before enrollment for all subjects who did not die prior to enrollment. We compared exposure-disease associations in each inception cohort to those in corresponding survivor cohorts to determine how different assumptions impacted bias in the survivor cohorts. All subjects in both inception and survivor cohorts were considered equally susceptible to the effect of exposure in causing disease. We used Cox proportional hazards regression to calculate effect measures. There was no bias in survivor cohort estimates when case fatality among diseased subjects was independent of exposure. This was true even when the disease was highly fatal and more highly exposed subjects were more likely to develop disease and die. Assuming a positive exposure-response in the inception cohort, survivor cohort rate ratios were biased downwards when case fatality was greater with higher exposure. Survivor cohort effect estimates for fatal outcomes are not always biased, although precision can decrease. Copyright © 2015 Elsevier Inc. All rights reserved.

Early morning awakening and nonrestorative sleep are associated with increased minor non-fatal accidents during work and leisure time.

PubMed

Chiu, Hsiao-Yean; Wang, Mei-Yeh; Chang, Cheng-Kuei; Chen, Ching-Min; Chou, Kuei-Ru; Tsai, Jen-Chen; Tsai, Pei-Shan

2014-10-01

The relationship between a composite measure of insomnia and occupational or fatal accidents has been investigated previously; however, little is known regarding the effect of various insomnia symptoms on minor non-fatal accidents during work and leisure time. We investigated the predicting role of insomnia symptoms on minor non-fatal accidents during work and leisure time. Data from the 2005 Taiwan Social Development Trend Survey of 36,473 Taiwanese aged ≥18 years were analyzed in 2013. Insomnia symptoms, including difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA), and nonrestorative sleep (NRS) were investigated. A minor non-fatal accident was defined as any mishap such as forgetting to turn off the gas or faucets, accidental falls, and abrasions or cuts occurring during work and leisure time in the past month that do not require immediate medical attention. Multivariable logistic regression was performed to assess the odds ratios (ORs) and associated 95% confidence interval (CI) of minor non-fatal accidents (as a binary variable) for each insomnia symptom compared with those of people presenting no symptoms, while controlling for possible confounders. EMA and NRS increased the odds of minor non-fatal accidents occurring during work and leisure time (adjusted OR=1.19, 95% CI=1.08-1.32 and adjusted OR=1.27, 95% CI=1.17-1.37, respectively). EMA and NRS are two symptoms that are significantly associated with an increased likelihood of minor non-fatal accidents during work and leisure time after adjusting for of a range of covariates. Copyright © 2014 Elsevier Ltd. All rights reserved.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

PubMed

Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

2015-08-01

Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

Development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders.

PubMed

Burtnick, Mary N; Heiss, Christian; Roberts, Rosemary A; Schweizer, Herbert P; Azadi, Parastoo; Brett, Paul J

2012-01-01

Burkholderia pseudomallei and Burkholderia mallei, the etiologic agents of melioidosis and glanders, respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. Diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. At present, there are no human or veterinary vaccines available for immunization against these emerging/re-emerging infectious diseases. One of the long term objectives of our research, therefore, is to identify and characterize protective antigens expressed by B. pseudomallei and B. mallei and use them to develop efficacious vaccine candidates. Previous studies have demonstrated that the 6-deoxy-heptan capsular polysaccharide (CPS) expressed by these bacterial pathogens is both a virulence determinant and a protective antigen. Consequently, this carbohydrate moiety has become an important component of the various subunit vaccines that we are currently developing in our laboratory. In the present study, we describe a reliable method for isolating CPS antigens from O-polysaccharide (OPS) deficient strains of B. pseudomallei; including a derivative of the select agent excluded strain Bp82. Utilizing these purified CPS samples, we also describe a simple procedure for covalently linking these T-cell independent antigens to carrier proteins. In addition, we demonstrate that high titer IgG responses can be raised against the CPS component of such constructs. Collectively, these approaches provide a tangible starting point for the development of novel CPS-based glycoconjugates for immunization against melioidosis and glanders.

Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

PubMed

Jiménez-Morales, Silvia; Ramírez-Florencio, Mireya; Mejía-Aranguré, Juan Manuel; Núñez-Enríquez, Juan Carlos; Bekker-Mendez, Carolina; Torres-Escalante, José Luis; Flores-Lujano, Janet; Jiménez-Hernández, Elva; Del Carmen Rodríguez-Zepeda, María; Leal, Yelda A; González-Montalvo, Pablo Miguel; Pantoja-Guillen, Francisco; Peñaloza-Gonzalez, José Gabriel; Gutiérrez-Juárez, Erick Israel; Núñez-Villegas, Nora Nancy; Pérez-Saldivar, Maria Luisa; Guerra-Castillo, Francisco Xavier; Flores-Villegas, Luz Victoria; Ramos-Cervantes, María Teresa; Fragoso, José Manuel; García-Escalante, María Guadalupe; Del Carmen Pinto-Escalante, Doris; Ramírez-Bello, Julián; Hidalgo-Miranda, Alfredo

2016-11-01

It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Temporal distribution of trauma deaths: quality of trauma care in a developing country.

PubMed

Masella, Cesar Augusto; Pinho, Vitor Ferreira; Costa Passos, Afonso Dinis; Spencer Netto, Fernando A C; Rizoli, Sandro; Scarpelini, Sandro

2008-09-01

Examination of the epidemiology and timing of trauma deaths has been deemed a useful method to evaluate the quality of trauma care. The purpose of this study was to evaluate the quality of trauma care in a regional trauma system and in a university hospital in Brazil by comparing the timing of deaths in the studied prehospital and in-hospital settings to those published for trauma systems in other areas. We analyzed the National Health Minister's System of Deaths Information for the prehospital mortality and we retrospectively collected the demographics, timelines, and trauma severity scores of all in-hospital patients who died after admission through the Emergency Unit of Hospital das Clinicas de Ribeirao Preto between 2000 and 2001. During the study period, there were 787 trauma fatalities in the city: 448 (56.9%) died in the prehospital setting and 339 (43.1%) died after being admitted to a medical facility. In 2 years, 238 trauma deaths occurred in the studied hospital, and we found a complete clinical set of data for 224 of these patients. The majority of deaths in the prehospital setting were caused by penetrating injuries (66.7%), whereas in-hospital mortality was mainly because of blunt traumas (59.1%). The largest number of in-hospital deaths occurred beyond 72 hours of stay (107 patients-47%). The region studied showed some deficiencies in prehospital and in-hospitals settings, in particular in the critical care and short-term follow-up of trauma patients when compared with the literature. Particularly, the late mortality may be related to training and human resources deficiency. Based on the timeline of trauma deaths, we can suggest that the studied region needs improvements in the prehospital trauma system and in hospital critical care.

Development of a SARS Coronavirus Vaccine from Recombinant Spike Protein Plus Delta Inulin Adjuvant.

PubMed

McPherson, Clifton; Chubet, Richard; Holtz, Kathy; Honda-Okubo, Yoshikazu; Barnard, Dale; Cox, Manon; Petrovsky, Nikolai

2016-01-01

Given periodic outbreaks of fatal human infections caused by coronaviruses, development of an optimal coronavirus vaccine platform capable of rapid production is an ongoing priority. This chapter describes the use of an insect cell expression system for rapid production of a recombinant vaccine against severe acute respiratory syndrome coronavirus (SARS). Detailed methods are presented for expression, purification, and release testing of SARS recombinant spike protein antigen, followed by adjuvant formulation and animal testing. The methods herein described for rapid development of a highly protective SARS vaccine are equally suited to rapid development of vaccines against other fatal human coronavirus infections, e.g., the MERS coronavirus.

[The activity of local health units in agriculture: promotion, prevention, control].

PubMed

Angotzi, G; Ariano, E; Quercia, A

2010-01-01

Agriculture shows an high proportion of injuries, mostly by machineries and instruments, and the highest proportion between fatal and total injuries. The Conference of Regions has adopted the National Agriculture and Forestry Prevention Plan, in application of the "Pact for health and safety in workplaces". The plan gives priority to actions improving the safety of agricultural machines, specially if more frequently involved in serious and fatal injuries. Goal is to achieve an homogenous intervention standard all over in the country, composed by a mix of information, support and control, addressed to farms and agricultural machines traders. Public prevention organizations of Local Health Units moreover will record homogenously the happen modality of fatal and serious accidents, will collaborate in joining prevention objectives with Rural Develop Plans and in drawing up good practices. At another level in some regions have been developed prevention activities for other risk factors: definition of exposition profiles of pesticides, development of professionally exposed workers formation, control of buildings and cattle breeding, medical and epidemiological periodic survey of employees.

Developing a Model for Forecasting Road Traffic Accident (RTA) Fatalities in Yemen

NASA Astrophysics Data System (ADS)

Karim, Fareed M. A.; Abdo Saleh, Ali; Taijoobux, Aref; Ševrović, Marko

2017-12-01

The aim of this paper is to develop a model for forecasting RTA fatalities in Yemen. The yearly fatalities was modeled as the dependent variable, while the number of independent variables included the population, number of vehicles, GNP, GDP and Real GDP per capita. It was determined that all these variables are highly correlated with the correlation coefficient (r ≈ 0.9); in order to avoid multicollinearity in the model, a single variable with the highest r value was selected (real GDP per capita). A simple regression model was developed; the model was very good (R2=0.916); however, the residuals were serially correlated. The Prais-Winsten procedure was used to overcome this violation of the regression assumption. The data for a 20-year period from 1991-2010 were analyzed to build the model; the model was validated by using data for the years 2011-2013; the historical fit for the period 1991 - 2011 was very good. Also, the validation for 2011-2013 proved accurate.

Cytokine response signatures in disease progression and development of severe clinical outcomes for leptospirosis.

PubMed

Reis, Eliana A G; Hagan, José E; Ribeiro, Guilherme S; Teixeira-Carvalho, Andrea; Martins-Filho, Olindo A; Montgomery, Ruth R; Shaw, Albert C; Ko, Albert I; Reis, Mitermayer G

2013-01-01

The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS). We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not. This study shows that severe cases of leptospirosis are differentiated from mild disease by a "cytokine storm" process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.

Fleet Safety: Developing & Sustaining an Effective Program With ANSI/ASSE Z15.1.

PubMed

Hammer, Brian S; Pratt, Stephanie G; Ross, Peggy

2014-03-01

Millions of U.S. workers are at risk for a work-related motor vehicle crash. Fatality data show that across all industries, motor vehicle crashes are consistently the leading cause of work-related fatalities. Of 43,025 work-related fatalities reported by BLS between 2003 and 2010, 10,202 were the result of single- or multiple-vehicle crashes of workers driving or riding in a vehicle on a public roadway, and 2,707 were pedestrian workers struck by a motor vehicle. During the same period, an additional 2,487 workers died in crashes that occurred off a public roadway or on industrial premises (BLS, 2013).

Passive immunization with Leptospira LPS-specific agglutinating but not non-agglutinating monoclonal antibodies protect guinea pigs from fatal pulmonary hemorrhages induced by serovar Copenhageni challenge.

PubMed

Challa, Sreerupa; Nally, Jarlath E; Jones, Carroll; Sheoran, Abhineet S

2011-06-15

Leptospira interrogans serovar Copenhageni causes pulmonary hemorrhages with respiratory failure, a major cause of death in leptospirosis patients. Protective immunity to Leptospira is known to correlate with the production of leptospiral lipopolysaccharide (L-LPS)-specific agglutinating antibodies. We generated L-LPS-specific mouse monoclonal antibodies (MAbs) and investigated if these MAbs can protect guinea pigs against fatal pulmonary hemorrhages caused by serovar Copenhageni. The MAbs L8H4 and L9B11 against 22kDa L-LPS agglutinated leptospires and completely protected guinea pigs from the development of fatal pulmonary hemorrhages by serovar Copenhageni, whereas the MAb L4C1 against 8kDa L-LPS neither agglutinated the bacteria nor protected the animals against the fatal pulmonary hemorrhages. Copyright © 2011 Elsevier Ltd. All rights reserved.

A novel risk assessment method for landfill slope failure: Case study application for Bhalswa Dumpsite, India.

PubMed

Jahanfar, Ali; Amirmojahedi, Mohsen; Gharabaghi, Bahram; Dubey, Brajesh; McBean, Edward; Kumar, Dinesh

2017-03-01

Rapid population growth of major urban centres in many developing countries has created massive landfills with extraordinary heights and steep side-slopes, which are frequently surrounded by illegal low-income residential settlements developed too close to landfills. These extraordinary landfills are facing high risks of catastrophic failure with potentially large numbers of fatalities. This study presents a novel method for risk assessment of landfill slope failure, using probabilistic analysis of potential failure scenarios and associated fatalities. The conceptual framework of the method includes selecting appropriate statistical distributions for the municipal solid waste (MSW) material shear strength and rheological properties for potential failure scenario analysis. The MSW material properties for a given scenario is then used to analyse the probability of slope failure and the resulting run-out length to calculate the potential risk of fatalities. In comparison with existing methods, which are solely based on the probability of slope failure, this method provides a more accurate estimate of the risk of fatalities associated with a given landfill slope failure. The application of the new risk assessment method is demonstrated with a case study for a landfill located within a heavily populated area of New Delhi, India.

What can flies tell us about copper homeostasis?

PubMed

Southon, Adam; Burke, Richard; Camakaris, James

2013-10-01

Copper (Cu) is an essential redox active metal that is potentially toxic in excess. Multicellular organisms acquire Cu from the diet and must regulate uptake, storage, distribution and export of Cu at both the cellular and organismal levels. Systemic Cu deficiency can be fatal, as seen in Menkes disease patients. Conversely Cu toxicity occurs in patients with Wilson disease. Cu dyshomeostasis has also been implicated in neurodegenerative disorders such as Alzheimer's disease. Over the last decade, the fly Drosophila melanogaster has become an important model organism for the elucidation of eukaryotic Cu regulatory mechanisms. Gene discovery approaches with Drosophila have identified novel genes with conserved protein functions relevant to Cu homeostasis in humans. This review focuses on our current understanding of Cu uptake, distribution and export in Drosophila and the implications for mammals.

Assignment of Etfdh, Etfb, and Etfa to chromosomes 3, 7, and 13: The mouse homologs of genes respondible for glutaric acidemia type II in human

DOE Office of Scientific and Technical Information (OSTI.GOV)

White, R.A.; Dowler, L.L.; Angeloni, S.V.

Electron transfer flavoprotein (composed of {alpha} and {beta} subunits) is an obligatory electron acceptor for several dehydrogenases and is located in the mitochondrial matrix. Electrons accepted by electron transfer flavo-protein (ETF) are transferred to the main mitochondrial respiratory chain by the way of ETF dehydrogenase (ETFDH). In humans, deficiency of ETF or ETFDH leads to glutaric acidemia type II, an inherited metabolic disorder that can be fatal in its neonatal form and is characterized by severe hypoketotic hypoglycemia and acidosis. We used cDNA probes for the Etfdh, Etfb, and Etfa genes to determine localization of these mouse genes to chromosomesmore » 3, 7, and 13. 18 refs., 3 figs.« less

Optimization study of direct morphology observation by cold field emission SEM without gold coating.

PubMed

He, Dan; Fu, Cheng; Xue, Zhigang

2018-06-01

Gold coating is a general operation that is generally applied on non-conductive or low conductive materials, during which the morphology of the materials can be examined by scanning electron microscopy (SEM). However, fatal deficiencies in the materials can result in irreversible distortion and damage. The present study directly characterized different low conductive materials such as hydroxyapatite, modified poly(vinylidene fluoride) (PVDF) fiber, and zinc oxide nanopillar by cold field emission scanning electron microscopy (FE-SEM) without a gold coating. According to the characteristics of the low conductive materials, various test conditions, such as different working signal modes, accelerating voltages, electron beam spots, and working distances, were characterized to determine the best morphological observations of each sample. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pathologies of the digestive system caused by marine debris in Chelonia mydas.

PubMed

Jerdy, Hassan; Werneck, Max Rondon; da Silva, Maria Aparecida; Ribeiro, Rachel Bittencourt; Bianchi, Mariah; Shimoda, Eduardo; de Carvalho, Eulógio Carlos Queiróz

2017-03-15

The growth of human population and deficient pollution control measures pose significant challenge to the environment. Despite conservation efforts, all sea turtle species are at some risk of extinction. The present study investigated the effect of marine debris on the gastrointestinal tract of green turtles in southeastern Brazil. Of the 777 animals evaluated, 290 showed marine debris in one segment of the gastrointestinal tract. The presence of these materials in the gastrointestinal tract may be harmful, independent of the segment involved, and increases the risk of impaction. Marine debris has become a significant hazard to Chelonia mydas in the region surveyed, causing perforation, rupture, or fecal impaction that, when not treated, is potentially fatal, exposing the intestine to bacterial infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prune Belly syndrome: A rare case report

PubMed Central

Samal, Sunil Kumar; Rathod, Setu

2015-01-01

Prune Belly syndrome (PBS) is a rare congenital anomaly of uncertain etiology almost exclusive to males. We report a case of term male baby born to a 39-year-old grand multipara with previous four normal vaginal births. There was no history of genetic or congenital anomaly in her family. Examination of the baby revealed hypotonia, deficient abdominal muscle, cryptorchidism, palpable kidney, and bladder. Ultrasound examination of the abdomen revealed bilateral gross hydronephrosis and megaureter. Provisional diagnosis of PBS was made and the baby was admitted in neonatal intensive care units for further management. Routine antenatal care with ultrasonography will help in detecting renal anomalies, which can be followed postnatally. Early diagnosis of this syndrome and determining its optimal treatment are very important in helping to avoid its fatal course. PMID:25810678

Wernicke-Korsakoff syndrome in the course of thyrotoxicosis - a case report.

PubMed

Wierzbicka-Chmiel, Joanna; Wierzbicki, Krzysztof; Kajdaniuk, Dariusz; Sędziak, Ryszard; Marek, Bogdan

2011-01-01

Wernicke-Korsakoff syndrome (also called Wernicke's encephalopathy) is a potentially fatal, neuropsychiatric syndrome caused most frequently by thiamine deficiency. The three classic symptoms found together are confusion, ataxia and eyeball manifestations. Memory disturbances can also be symptoms. Wernicke's encephalopathy mainly results from alcohol abuse, but also from malnutrition, cancer, chronic dialysis, thyrotoxicosis and, in well-founded cases, encephalopathy associated with autoimmune thyroid disease (EAATD). The coexistence of many factors makes a proper diagnosis difficult, delays appropriate treatment and consequently reduces the chance of complete recovery. We present the case of a 53 year-old female with Wernicke's encephalopathy caused by chronic malnutrition, surgical operation, as well as thyrotoxicosis. She received treatment with intravenous thiamine administration and also anti-thyroid treatment which caused satisfactory regression of her neurological symptoms.

Hepcidin-25 is related to cardiovascular events in chronic haemodialysis patients.

PubMed

van der Weerd, Neelke C; Grooteman, Muriel P C; Bots, Michiel L; van den Dorpel, Marinus A; den Hoedt, Claire H; Mazairac, Albert H A; Nubé, Menso J; Penne, E Lars; Wetzels, Jack F M; Wiegerinck, Erwin T; Swinkels, Dorine W; Blankestijn, Peter J; Ter Wee, Piet M

2013-12-01

The development of atherosclerosis may be enhanced by iron accumulation in macrophages. Hepcidin-25 is a key regulator of iron homeostasis, which downregulates the cellular iron exporter ferroportin. In haemodialysis (HD) patients, hepcidin-25 levels are increased. Therefore, it is conceivable that hepcidin-25 is associated with all-cause mortality and/or fatal and non-fatal cardiovascular (CV) events in this patient group. The aim of the current analysis was to study the relationship between hepcidin-25 and all-cause mortality and both fatal and non-fatal CV events in chronic HD patients. Data from 405 chronic HD patients included in the CONvective TRAnsport STudy (NCT00205556) were studied (62% men, age 63.7 ± 13.9 years [mean ± SD]). The median (range) follow-up was 3.0 (0.8-6.6) years. Hepcidin-25 was measured with mass spectrometry. The relationship between hepcidin-25 and all-cause mortality or fatal and non-fatal CV events was investigated with multivariate Cox proportional hazard models. Median (interquartile range) hepcidin-25 level was 13.8 (6.6-22.5) nmol/L. During follow-up, 158 (39%) patients died from any cause and 131 (32%) had a CV event. Hepcidin-25 was associated with all-cause mortality in an unadjusted model [hazard ratio (HR) 1.14 per 10 nmol/L, 95% CI 1.03-1.26; P = 0.01], but not after adjustment for all confounders including high-sensitive C-reactive protein (HR 1.02 per 10 nmol/L, 95% CI 0.87-1.20; P = 0.80). At the same time, hepcidin-25 was significantly related to fatal and non-fatal CV events in a fully adjusted model (HR 1.24 per 10 nmol/L, 95% CI 1.05-1.46, P = 0.01). Hepcidin-25 was associated with fatal and non-fatal CV events, even after adjustment for inflammation. Furthermore, inflammation appears to be a significant confounder in the relation between hepcidin-25 and all-cause mortality. These findings suggest that hepcidin-25 might be a novel determinant of CV disease in chronic HD patients.

V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis.

PubMed

Valls Serón, Mercedes; Ferwerda, Bart; Engelen-Lee, JooYeon; Geldhoff, Madelijn; Jaspers, Valery; Zwinderman, Aeilko H; Tanck, Michael W; Baas, Frank; van der Ende, Arie; Brouwer, Matthijs C; van de Beek, Diederik

2016-05-18

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningitis.

The quality of the maternal health system in Eritrea.

PubMed

Sharan, Mona; Ahmed, Saifuddin; Ghebrehiwet, Mismay; Rogo, Khama

2011-12-01

To examine the quality of the maternal health system in Eritrea to understand system deficiencies and its relevance to maternal mortality within the context of Millennium Development Goal (MDG) 5. A sample of 118 health facilities was surveyed. Data were collected on 5 dimensions of health system quality: availability; accessibility; management; infrastructure; and process indicators. Data on the causes of hospital admissions for obstetric patients and maternal deaths were extracted from medical records. Eritrea has only 11 comprehensive emergency obstetric care (CEmOC) facilities, all of which are grossly understaffed. There is considerable pressure on the infrastructure and health providers at hospitals. Compliance with clinical care standards and availability of supplies were optimal. As a result, the case fatality rate of 0.65% was low. In total, 45.6% of obstetric admissions and 19.5% of maternal deaths were attributed to abortion complications. In Eritrea, critical gaps in the health system-especially those related to human resources-will impede progress toward MDG 5, and it will not be possible to reduce maternal mortality without addressing the high burden of abortion. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

PubMed Central

Truong, Lisa; Barton, Carrie L.; Chase, Tyler T.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

2017-01-01

Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa) were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes. PMID:28837703

TOXOPLASMOSIS—The Protean Manifestations of the Condition and Their Significance in Pregnancy and in Newborn Infants

PubMed Central

Hoyt, Robert S.

1963-01-01

Toxoplasmosis is a relatively common and generally mild parasitic infection which can, however, produce fatal and crippling complications under certain conditions — particularly when a human fetus or a newborn infant is infected. In this instance, the infection is the result of a spread of the acquired disease which may occur in the mother in the last six months of pregnancy. Although the infection of adults can be dangerous and fatalities have been reported, the danger to the nervous system, eyes and other structures of the newborn infant can be devastating—blindness, brain damage and mental deficiency, particularly as the result of an obstruction to the flow of circulating cerebrospinal fluid within the brain. This report covers a number of differing features of the disease which have been described separately by other authors in specialty journals and in the foreign literature. If present, these signs should suggest toxoplasmosis, particularly in pregnancy, in the newborn infant and in still-born infants. Early diagnosis is of paramount interest in view of the poor response which may be obtained in the treatment of subacute and chronic phases of the illness. Difficulties in diagnosis stem from the manifestations of toxoplasmosis which closely resemble the symptoms of other infectious diseases. The clinical laboratory diagnosis is made by the isolation of the organism or by the demonstration of immune protein in the patient's serum. PMID:13955214

Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome.

PubMed

Chen, Byron; Hui, Jessica; Montgomery, Kelsey S; Gella, Alejandro; Bolea, Irene; Sanz, Elisenda; Palmiter, Richard D; Quintana, Albert

2017-01-01

Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4 , a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs), which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

Fatigue failure of metal components as a factor in civil aircraft accidents

NASA Technical Reports Server (NTRS)

Holshouser, W. L.; Mayner, R. D.

1972-01-01

A review of records maintained by the National Transportation Safety Board showed that 16,054 civil aviation accidents occurred in the United States during the 3-year period ending December 31, 1969. Material failure was an important factor in the cause of 942 of these accidents. Fatigue was identified as the mode of the material failures associated with the cause of 155 accidents and in many other accidents the records indicated that fatigue failures might have been involved. There were 27 fatal accidents and 157 fatalities in accidents in which fatigue failures of metal components were definitely identified. Fatigue failures associated with accidents occurred most frequently in landing-gear components, followed in order by powerplant, propeller, and structural components in fixed-wing aircraft and tail-rotor and main-rotor components in rotorcraft. In a study of 230 laboratory reports on failed components associated with the cause of accidents, fatigue was identified as the mode of failure in more than 60 percent of the failed components. The most frequently identified cause of fatigue, as well as most other types of material failures, was improper maintenance (including inadequate inspection). Fabrication defects, design deficiencies, defective material, and abnormal service damage also caused many fatigue failures. Four case histories of major accidents are included in the paper as illustrations of some of the factors invovled in fatigue failures of aircraft components.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

PubMed

Holman, Rury R; Coleman, Ruth L; Chan, Juliana C N; Chiasson, Jean-Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J; Tendera, Michal; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu

2017-11-01

The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009, and Oct 23, 2015, 6522 patients were randomly assigned and included in the intention-to-treat population, 3272 assigned to acarbose and 3250 to placebo. Patients were followed up for a median of 5·0 years (IQR 3·4-6·0) in both groups. The primary five-point composite outcome occurred in 470 (14%; 3·33 per 100 person-years) of 3272 acarbose group participants and in 479 (15%; 3·41 per 100 person-years) of 3250 placebo group participants (hazard ratio 0·98; 95% CI 0·86-1·11, p=0·73). No significant differences were seen between treatment groups for the secondary three-point composite outcome, death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, or impaired renal function. Diabetes developed less frequently in the acarbose group (436 [13%] of 3272; 3·17 per 100 person-years) compared with the placebo group (513 [16%] of 3250; 3·84 per 100 person-years; rate ratio 0·82, 95% CI 0·71-0·94, p=0·005). Gastrointestinal disorders were the most common adverse event associated with drug discontinuation or dose changes (215 [7%] of 3263 patients in the acarbose group vs 150 [5%] of 3241 in the placebo group [p=0·0007]; safety population). Numbers of non-cardiovascular deaths (71 [2%] of 3272 vs 56 [2%] of 3250, p=0·19) and cancer deaths (ten [<1%] of 3272 vs 12 [<1%] of 3250, p=0·08) did not differ between groups. In Chinese patients with coronary heart disease and impaired glucose tolerance, acarbose did not reduce the risk of major adverse cardiovascular events, but did reduce the incidence of diabetes. Bayer AG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fatal and non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone.

PubMed

Kelty, Erin; Hulse, Gary

2017-08-01

Illicit opioid use is associated with high rates of fatal and non-fatal opioid overdose. This study aims to compare rates of fatal and serious but non-fatal opioid overdose in opioid dependent patients treated with methadone, buprenorphine or implant naltrexone, and to identify risk factors for fatal opioid overdose. Opioid dependent patients treated with methadone (n=3515), buprenorphine (n=3250) or implant naltrexone (n=1461) in Western Australia for the first time between 2001 and 2010, were matched against state mortality and hospital data. Rates of fatal and non-fatal serious opioid overdoses were calculated and compared for the three treatments. Risk factors associated with fatal opioid overdose were examined using multivariate cox proportional hazard models. No significant difference was observed between the three groups in terms of crude rates of fatal or non-fatal opioid overdoses. During the first 28days of treatment, rates of non-fatal opioid overdose were high in all three groups, as were fatal opioid overdoses in patients treated with methadone. However, no fatal opioid overdoses were observed in buprenorphine or naltrexone patients during this period. Following the first 28 days, buprenorphine was shown to be protective, particularly in terms of non-fatal opioid overdoses. After the cessation of treatment, rates of fatal and non-fatal opioid overdoses were similar between the groups, with the exception of lower rates of non-fatal opioid overdose in the naltrexone treated patients compared with the methadone treated patients. After the commencement of treatment, gender, and hospitalisations with a diagnosis of opioid poisoning, cardiovascular or mental health problems were significant predictors of subsequent fatal opioid overdose. Rates of fatal and non-fatal opioid overdose were not significantly different in patients treated with methadone, buprenorphine or implant naltrexone. Gender and prior cause-specific hospitalisations can be used to identify patients at a high risk of fatal opioid overdose. Copyright © 2017 Elsevier B.V. All rights reserved.

Rising gasoline prices increase new motorcycle sales and fatalities.

PubMed

Zhu, He; Wilson, Fernando A; Stimpson, Jim P; Hilsenrath, Peter E

2015-12-01

We examined whether sales of new motorcycles was a mechanism to explain the relationship between motorcycle fatalities and gasoline prices. The data came from the Motorcycle Industry Council, Energy Information Administration and Fatality Analysis Reporting System for 1984-2009. Autoregressive integrated moving average (ARIMA) regressions estimated the effect of inflation-adjusted gasoline price on motorcycle sales and logistic regressions estimated odds ratios (ORs) between new and old motorcycle fatalities when gasoline prices increase. New motorcycle sales were positively correlated with gasoline prices (r = 0.78) and new motorcycle fatalities (r = 0.92). ARIMA analysis estimated that a US$1 increase in gasoline prices would result in 295,000 new motorcycle sales and, consequently, 233 new motorcycle fatalities. Compared to crashes on older motorcycle models, those on new motorcycles were more likely to be young riders, occur in the afternoon, in clear weather, with a large engine displacement, and without alcohol involvement. Riders on new motorcycles were more likely to be in fatal crashes relative to older motorcycles (OR 1.14, 95 % confidence interval (CI) 1.02-1.28) when gasoline prices increase. Our findings suggest that, in response to increasing gasoline prices, people tend to purchase new motorcycles, and this is accompanied with significantly increased crash risk. There are several policy mechanisms that can be used to lower the risk of motorcycle crash injuries through the mechanism of gas prices and motorcycle sales such as raising awareness of motorcycling risks, enhancing licensing and testing requirements, limiting motorcycle power-to-weight ratios for inexperienced riders, and developing mandatory training programs for new riders.

Fatal road traffic injuries in Ibadan, using the mortuary as a data source.

PubMed

Eze, Uwom O; Kipsaina, Chebiwot Caroline; Ozanne-Smith, Joan

2013-12-01

Road Traffic Injury (RTI) in Africa represents 14% of global RTI deaths. Lack of timely, reliable data undermines road safety interventions. Available fatality data are aggregated, limited in detail or scarce in surveys. This is the first fatal RTI surveillance study in Nigeria. To pilot a systematic mortuary-based data collection in Ibadan, determine the nature and circumstances of fatal RTI and assess data quality against existing data sources. Using a draft data collection system developed jointly by WHO and Monash University, the detailed information was prospectively collected on RTI University College Hospital mortuary admissions in Ibadan September 2010 to February 2011. Demographics, road user type, counterpart vehicle, intent, manner and medical cause of death were recorded. Mortuary admissions included 80 fatal RTI cases: 81.3% males. By road user category, 28 (35.0%) were pedestrians; 28 (35.0%) motorised 2-wheeler users; 18.8% car occupants; and 11.3% bus occupants. In 70% of cases, medical cause of death was head injury, including 25 of 28 motorised 2-wheeler users (89.3%). Estimates from this study indicate apparent increased mortuary capture of fatal RTI compared with police data. This study demonstrates the feasibility of collecting detailed, timely RTI fatality data through mortuary-based surveillance in Ibadan. While not all RTI deaths are reported to any authority in Ibadan, this large case series complements existing data sources and suggests that pedestrians and motorised 2-wheeler users die most often in road traffic crashes. Frequent head injuries among motorised 2-wheeler users strongly support the need for helmet wearing interventions.

Injury Deaths Among U.S. Females: CDC Resources and Programs

PubMed Central

Mack, Karin A.; Peterson, Cora; Zhou, Chao; MacConvery, Elliane; Wilkins, Natalie

2017-01-01

Injury death rates are lower for women than for men at all ages, but we have a long way to go in understanding the circumstances of injury fatalities among females. This article presents resources that can be used to examine the most recent data on injury fatalities among females and highlights activities of CDC’s Injury Center. The National Center for Injury Prevention and Control’s (NCIPC’s) Web-based Injury Statistics Query and Reporting System, an online surveillance database, can be used to examine injury deaths. We present examples that show the 2015 number of female fatal injuries by age group and injury cause and method, as well as a 2008–2014 county-level map of female fatal injury rates. In 2015, there were 68,572 injury fatalities of females of age ≥1 year, equivalent to 1 death every 7 minutes. Injuries were the leading cause of death for females of ages 1–41 years and the sixth-ranked cause of female death overall. Falls were the leading cause of injury death overall (and for women ≥70 years), unintentional poisonings were second, and motor vehicle traffic injuries were third. NCIPC funds national organizations, state health agencies, and other groups to develop, implement, and promote effective injury and violence prevention and control practices. Five key programs are discussed. Presenting data on injury fatalities is an essential element in identifying meaningful prevention efforts. Further investigation of the causes and impact of female injury fatalities can refine the public health approach to reduce this injury burden. PMID:28294691

Reported traumatic injuries among West Coast Dungeness crab fishermen, 2002-2014.

PubMed

Case, Samantha; Bovbjerg, Viktor; Lucas, Devin; Syron, Laura; Kincl, Laurel

2015-01-01

Commercial fishing is a high-risk occupation. The West Coast Dungeness crab fishery has a high fatality rate; however, nonfatal injuries have not been previously studied. The purpose of this report was to describe the characteristics of fatal and nonfatal traumatic occupational injuries and associated hazards in this fleet during 2002-2014. Data on fatal injuries were obtained from a surveillance system managed by the National Institute for Occupational Safety and Health. Data on nonfatal injuries were manually abstracted from Coast Guard investigation reports and entered into a study database. Descriptive statistics were used to characterise demographics, injury characteristics, and work processes performed. Twenty-eight fatal and 45 nonfatal injuries were reported between 2002 and 2014 in the Dungeness crab fleet. Most fatalities were due to vessel disasters, and many nonfatal injuries occurred on-deck when fishermen were working with gear, particularly when hauling the gear (47%). The most frequently reported injuries affected the upper extremities (48%), and fractures were the most commonly reported injury type (40%). The overall fatality rate during this time period was 209 per 100,000 full-time equivalent workers and the rate of nonfatal injury was 3.4 per 1,000 full-time equivalent workers. Dungeness crab fishermen are at relatively high risk for fatal injuries. Nonfatal injuries were limited to reported information, which hampers efforts to accurately estimate nonfatal injury risk and understand fishing hazards. Further research is needed to identify work tasks and other hazards that cause nonfatal injuries in this fleet. Engaging fishermen directly may help develop approaches for injury prevention.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

Evaluating the effectiveness of red light running camera enforcement in Cedar Rapids and developing guidelines for selection and use of red light running countermeasures.

DOT National Transportation Integrated Search

2011-11-01

Red light running (RLR) is a problem in the US that has resulted in 165,000 injuries and 907 fatalities annually. In Iowa, RLR-related crashes make up 24.5 percent of all crashes and account for 31.7 percent of fatal and major injury crashes at signa...

The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study.

PubMed

MacQueen, B C; Christensen, R D; Ward, D M; Bennett, S T; O'Brien, E A; Sheffield, M J; Baer, V L; Snow, G L; Weaver Lewis, K A; Fleming, R E; Kaplan, J

2017-04-01

Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay.

General dependencies and causality analysis of road traffic fatalities in OECD countries.

PubMed

Yaseen, Muhammad Rizwan; Ali, Qamar; Khan, Muhammad Tariq Iqbal

2018-05-07

The road traffic accidents were responsible for material and human loss which was equal to 2.8 to 5% of gross national product (GNP). However, literature does not explore the elasticity coefficients and nexus of road traffic fatalities with foreign direct investment, health expenditures, trade openness, mobile subscriptions, the number of researchers in R&D department, and environmental particulate matter. This study filled this research gap by exploring the nexus between road traffic fatalities, foreign direct investment, health expenditures, trade openness, mobile subscriptions, the number of researchers, and environmental particulate matter in Organization for Economic Cooperation and Development (OECD) countries by using panel data from 1995 to 2015. The panel Autoregressive Distributed Lag (ARDL) bound test was used for the detection of cointegration between the variables after checking the stationarity in selected variables with different panel unit root tests. Panel vector error correction model explored the causality of road traffic fatalities, foreign direct investment, PM2.5 in the environment, and trade openness in the long run. Road traffic fatalities showed short run bi-directional causality with foreign direct investment and health expenditures. The short run bi-directional causality was also observed between trade and foreign direct investment and cellular mobile subscriptions and foreign direct investment. The panel fully modified ordinary least square (FMOLS) and panel dynamic ordinary least square (DOLS) showed the 0.947% reduction in road fatalities for 1% increase in the health expenditures in OECD countries. The significant reduction in road fatalities was also observed due to 1% increase in trade openness and researchers in R&D, which implies the importance of trade and research for road safety. It is required to invest in the health sector for the safety of precious human lives like the hospitals with latest medical equipment and improvement in the emergency services in the country. The research and development activities should be enhanced especially for the health and transportation sectors. The trade of environment-friendly technology should be promoted for the protection of environment.

Alcohol use among fatally injured victims in São Paulo, Brazil: bridging the gap between research and health services in developing countries.

PubMed

Andreuccetti, Gabriel; Leyton, Vilma; Lemos, Nikolas P; Miziara, Ivan Dieb; Ye, Yu; Takitane, Juliana; Munoz, Daniel Romero; Reingold, Arthur L; Cherpitel, Cheryl J; de Carvalho, Heraclito Barbosa

2017-04-01

Most studies reporting alcohol use among fatally injured victims are subject to bias, particularly those related to sample selection and to absence of injury context data. We developed a research method to estimate the prevalence of alcohol consumption and test correlates of alcohol use prior to fatal injuries. Cross-sectional study based on a probability sample of fatally injured adult victims (n = 365) autopsied in São Paulo, Brazil. Victims were sampled within systematically selected 8-hour sampling blocks, generating a representative sample of fatal injuries occurring during all hours of the day for each day of the week between June 2014 and December 2015. The presence of alcohol and blood alcohol concentration (BAC) were the primary outcomes evaluated according to victims' socio-demographic, injury context data (type, day, time and injury place) and criminal history characteristics. Alcohol was detected in 30.1% [95% confidence interval (CI) = 25.6-35.1)] of the victims, with a mean blood alcohol level (BAC) level of 0.11% w/v (95% CI = 0.09-0.13) among alcohol-positive cases. Black and mixed race victims presented a higher mean BAC than white victims (P = 0.03). Fewer than one in every six suicides tested positive for alcohol, while almost half of traffic-related casualties were alcohol-positive. Having suffered traffic-related injuries, particularly those involving vehicle crashes, and injuries occurring during weekends and at night were associated significantly with alcohol use before injury (P < 0.05). Nearly one-third of fatal injuries in São Paulo between June 2014 and December 2015 were alcohol-related, with traffic accidents showing a greater association with alcohol use than other injuries. The sampling methodology tested here, including the possibility of adding injury context data to improve population-based estimates of alcohol use before fatal injury, appears to be a reliable and lower-cost strategy for avoiding biases common in death investigations. © 2016 Society for the Study of Addiction.

ALCOHOL USE AMONG FATALLY INJURED VICTIMS IN SAO PAULO, BRAZIL: BRIDGING THE GAP BETWEEN RESEARCH AND HEALTH SERVICES IN DEVELOPING COUNTRIES

PubMed Central

Andreuccetti, Gabriel; Leyton, Vilma; Lemos, Nikolas P.; Miziara, Ivan Dieb; Ye, Yu; Takitane, Juliana; Munoz, Daniel Romero; Reingold, Arthur L.; Cherpitel, Cheryl J.; de Carvalho, Heraclito Barbosa

2016-01-01

Background and aims Most studies reporting alcohol use among fatally injured victims are subject to bias, particularly that related to sample selection and to absence of injury context data. We developed a research method to estimate the prevalence of alcohol consumption and test correlates of alcohol use prior to fatal injuries, using the city of Sao Paulo, Brazil as a model. Design, Setting and Participants Cross-sectional study based on a probability sample of fatally injured adult victims (N=365) autopsied in Sao Paulo, Brazil. Victims were sampled within systematically selected 8-hour sampling blocks, generating a representative sample of fatal injuries occurring during all hours of the day for each day of the week between June 2014 and December 2015. Measurements The presence of alcohol and blood alcohol concentration (BAC) were the primary outcomes evaluated according to victims’ socio-demographic, injury context data (type, day, time and injury place), and criminal history characteristics. Findings Alcohol was detected in 30.1% (CI 95%; 25.6–35.1) of the victims, with a mean BAC level of 0.11% w/v (CI 95%; 0.09–0.13) among alcohol-positive cases. Those black and mixed race presented a higher mean BAC than white victims (p=0.03). Less than one in every six suicides tested positive for alcohol, while almost half of traffic-related casualties were alcohol-positive. Having suffered traffic-related injuries, particularly those involving vehicle crashes, and injuries occurring during weekends and at night were significantly associated with alcohol use before injury (p<0.05). Conclusions Nearly one third of fatal injuries in Sao Paulo were alcohol-related, with traffic accidents showing a greater association with alcohol use than other injuries. The sampling methodology tested here, including the possibility of adding injury context data to improve population-based estimates of alcohol use before fatal injury, was found to be a reliable and lower cost strategy for avoiding biases common in death investigations. PMID:28044383

Design of intelligent proximity detection zones to prevent striking and pinning fatalities around continuous mining machines.

PubMed

Bissert, P T; Carr, J L; DuCarme, J P; Smith, A K

2016-01-01

The continuous mining machine is a key piece of equipment used in underground coal mining operations. Over the past several decades these machines have been involved in a number of mine worker fatalities. Proximity detection systems have been developed to avert hazards associated with operating continuous mining machines. Incorporating intelligent design into proximity detection systems allows workers greater freedom to position themselves to see visual cues or avoid other hazards such as haulage equipment or unsupported roof or ribs. However, intelligent systems must be as safe as conventional proximity detection systems. An evaluation of the 39 fatal accidents for which the Mine Safety and Health Administration has published fatality investigation reports was conducted to determine whether the accident may have been prevented by conventional or intelligent proximity. Multiple zone configurations for the intelligent systems were studied to determine how system performance might be affected by the zone configuration. Researchers found that 32 of the 39 fatalities, or 82 percent, may have been prevented by both conventional and intelligent proximity systems. These results indicate that, by properly configuring the zones of an intelligent proximity detection system, equivalent protection to a conventional system is possible.

Innate immune response during herpes simplex virus encephalitis and development of immunomodulatory strategies.

PubMed

Piret, Jocelyne; Boivin, Guy

2015-09-01

Herpes simplex viruses are large double-stranded DNA viruses. These viruses have the ability to establish a lifelong latency in sensory ganglia and to invade and replicate in the CNS. Apart from relatively benign mucosal infections, HSV is responsible for severe illnesses including HSV encephalitis (HSE). HSE is the most common cause of sporadic, potentially fatal viral encephalitis in Western countries. If left untreated, the mortality rate associated with HSE is approximately 70%. Despite antiviral therapy, the mortality is still higher than 30%, and almost 60% of surviving individuals develop neurological sequelae. It is suggested that direct virus-related and indirect immune-mediated mechanisms contribute to the damages occurring in the CNS during HSE. In this manuscript, we describe the innate immune response to HSV, the development of HSE in mice knock-out for proteins of the innate immune system as well as inherited deficiencies in key components of the signaling pathways involved in the production of type I interferon that could predispose individuals to develop HSE. Finally, we review several immunomodulatory strategies aimed at modulating the innate immune response at a critical time after infection that were evaluated in mouse models and could be combined with antiviral therapy to improve the prognosis of HSE. In conclusion, the cerebral innate immune response that develops during HSE is a "double-edged sword" as it is critical to control viral replication in the brain early after infection, but, if left uncontrolled, may also result in an exaggerated inflammatory response that could be detrimental to the host. Copyright © 2015 John Wiley & Sons, Ltd.

Coenzyme Q biosynthesis in health and disease.

PubMed

Acosta, Manuel Jesús; Vazquez Fonseca, Luis; Desbats, Maria Andrea; Cerqua, Cristina; Zordan, Roberta; Trevisson, Eva; Salviati, Leonardo

2016-08-01

Coenzyme Q (CoQ, or ubiquinone) is a remarkable lipid that plays an essential role in mitochondria as an electron shuttle between complexes I and II of the respiratory chain, and complex III. It is also a cofactor of other dehydrogenases, a modulator of the permeability transition pore and an essential antioxidant. CoQ is synthesized in mitochondria by a set of at least 12 proteins that form a multiprotein complex. The exact composition of this complex is still unclear. Most of the genes involved in CoQ biosynthesis (COQ genes) have been studied in yeast and have mammalian orthologues. Some of them encode enzymes involved in the modification of the quinone ring of CoQ, but for others the precise function is unknown. Two genes appear to have a regulatory role: COQ8 (and its human counterparts ADCK3 and ADCK4) encodes a putative kinase, while PTC7 encodes a phosphatase required for the activation of Coq7. Mutations in human COQ genes cause primary CoQ(10) deficiency, a clinically heterogeneous mitochondrial disorder with onset from birth to the seventh decade, and with clinical manifestation ranging from fatal multisystem disorders, to isolated encephalopathy or nephropathy. The pathogenesis of CoQ(10) deficiency involves deficient ATP production and excessive ROS formation, but possibly other aspects of CoQ(10) function are implicated. CoQ(10) deficiency is unique among mitochondrial disorders since an effective treatment is available. Many patients respond to oral CoQ(10) supplementation. Nevertheless, treatment is still problematic because of the low bioavailability of the compound, and novel pharmacological approaches are currently being investigated. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016. Published by Elsevier B.V.

Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

PubMed

Martin, Nina M; Griffin, Diane E

2018-03-15

Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4 + T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10 -/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain. IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome. Copyright © 2018 American Society for Microbiology.

Vitamin A for the treatment of children with measles--a systematic review.

PubMed

D'Souza, Rennie M; D'Souza, Ron

2002-12-01

Vitamin A deficiency is a recognized risk factor for severe measles. WHO and UNICEF have recommended vitamin A for the treatment of measles but there are children still dying from measles. A systematic review, including the use of meta-analysis was done of randomized controlled trials comparing vitamin A with placebo obtained from a systematic search of the medical literature to determine whether vitamin A prevents mortality and pneumonia-specific mortality in children with measles. We identified five trials conducted in Africa, four in hospitals and one in a community that met the inclusion criteria. There were 445 children aged 6 months to 13 years supplemented with vitamin A and 478 with placebo. There was a 39 per cent reduction in overall mortality when vitamin A was used for the treatment of measles but this was not statistically significant (relative risk 0.61; 95 per cent confidence interval 0.32-1.12). When stratified by dose, 200 000 IU of vitamin A given for 2 days was associated with a reduction in overall mortality (0.36, 0.14-0.82) and pneumonia-specific mortality (0.33, 0.08-0.92) in hospitalized children in areas with high case fatality. Greater reduction in mortality was observed in children under the age of 2 years (0.17, 0.03-0.61). On the other hand, a single dose of 200 000 IU of vitamin A was not associated with reduced mortality (1.25, 0.48-3.1). There were no trials comparing a single dose with two doses of vitamin A. There were not enough studies to separate out the individual effects of age, dose, formulation, hospitalization and case fatality in the study area. We conclude that 200 000 IU of vitamin A repeated on 2 days should be used for the treatment of measles as recommended by WHO in children admitted to hospitals in areas where the case fatality is high.

Identification, Prevention and Treatment of Iron Deficiency during the First 1000 Days

PubMed Central

Burke, Rachel M.; Leon, Juan S.; Suchdev, Parminder S.

2014-01-01

Iron deficiency is a global problem across the life course, but infants and their mothers are especially vulnerable to both the development and the consequences of iron deficiency. Maternal iron deficiency during pregnancy can predispose offspring to the development of iron deficiency during infancy, with potentially lifelong sequelae. This review explores iron status throughout these “first 1000 days” from pregnancy through two years of age, covering the role of iron and the epidemiology of iron deficiency, as well as its consequences, identification, interventions and remaining research gaps. PMID:25310252

Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

PubMed

Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

2016-02-01

This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases.

Fatal neonatal-onset mitochondrial respiratory chain disease with T cell immunodeficiency.

PubMed

Reichenbach, Janine; Schubert, Ralf; Horvàth, Rita; Petersen, Jens; Fütterer, Nancy; Malle, Elisabeth; Stumpf, Andreas; Gebhardt, Boris R; Koehl, Ulrike; Schraven, Burkhart; Zielen, Stefan

2006-09-01

We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporo-occipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes II+III and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8(+) T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8(+) T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease.

Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenosine Phosphorylase (MTAP), an Exploitable Tumor Target

PubMed Central

Collins, Colin C; Volik, Stanislav V; Lapuk, Anna V; Wang, Yuwei; Gout, Peter W; Wu, Chunxiao; Xue, Hui; Cheng, Hongwei; Haegert, Anne; Bell, Robert H; Brahmbhatt, Sonal; Anderson, Shawn; Fazli, Ladan; Hurtado-Coll, Antonio; Rubin, Mark A.; Demichelis, Francesca; Beltran, Himisha; Hirst, Martin; Marra, Marco; Maher, Christopher A.; Chinnaiyan, Arul M.; Gleave, Martin; Bertino, Joseph R.; Lubin, Martin; Wang, Yuzhuo

2013-01-01

Castrate resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumour sequencing program, a patient tumour was analyzed using Illumina genome sequencing and a matched renal capsule tumour xenograft was generated. Both tumour and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2 and ARF genes. It is rare for this deletion to occur in primary prostate tumours yet approximately 10% express decreased levels of MTAP mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it appears that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers since deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumours at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology. PMID:22252602

Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting.

PubMed Central

Molyneux, Elizabeth; Ahmad, Shafique; Robertson, Ann

2006-01-01

PROBLEM: Early assessment, prioritization for treatment and management of sick children attending a health service are critical to achieving good outcomes. Many hospitals in developing countries see large numbers of patients and have few staff, so patients often have to wait before being assessed and treated. APPROACH: We present the example of a busy Under-Fives Clinic that provided outpatient services, immunizations and treatment for medical emergencies. The clinic was providing an inadequate service resulting in some inappropriate admissions and a high case-fatality rate. We assessed the deficiencies and sought resources to improve services. LOCAL SETTING: A busy paediatric outpatient clinic in a public tertiary care hospital in Blantyre, Malawi. RELEVANT CHANGES: The main changes we made were to train staff in emergency care and triage, improve patient flow through the department and to develop close cooperation between inpatient and outpatient services. Training coincided with a restructuring of the physical layout of the department. The changes were put in place when the department reopened in January 2001. LESSONS LEARNED: Improvements in the process and delivery of care and the ability to prioritize clinical management are essential to good practice. Making the changes described above has streamlined the delivery of care and led to a reduction in inpatient mortality from 10-18% before the changes were made (before 2001) to 6-8% after. PMID:16628305

Common causes of dyspnoea in athletes: a practical approach for diagnosis and management

PubMed Central

Mohseni, Zahra S.; Berwager, Jeffrey D.; Hegedus, Eric J.

2016-01-01

Key points “Dyspnoea” during exercise is a common complaint in seemingly otherwise healthy athletes, which may be associated with fatigue and underperformance. Because dyspnoea is an general term and may be caused by numerous factors, ranging from poor aerobic fitness to serious, potentially fatal respiratory and nonrespiratory pathologies, it is important for clinicians to obtain an appropriate case history and ask relevant exercise-specific questions to fully characterise the nature of the complaint so that a targeted diagnostic plan can be developed. Exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction are two common causes of dyspnoea in athletes, and both are regularly misdiagnosed and mismanaged due to poor adherence to available practice parameters. Aside from airway dysfunction, iron deficiency and anaemia, infectious disease, and musculoskeletal conditions are common problems in athletes which ultimately may lead to complaints of dyspnoea. Educational aims To inform readers of the common causes of dyspnoea encountered in athletes. To highlight that airway diseases, such as asthma and exercise-induced bronchoconstriction, are commonly misdiagnosed and mismanaged. To introduce readers to common nonairway causes of dyspnoea in athletes, including clinical features and general principles of diagnosis, and management. To emphasise the importance of a detailed case history and proper adherence to established protocols in evaluating and managing the dyspnoeic athlete. To provide readers with a general framework of appropriate questions that are useful for developing a targeted diagnostic plan for evaluating dyspnoeic athletes. Dyspnoea during exercise is a common chief complaint in athletes and active individuals. It is not uncommon for dyspnoeic athletes to be diagnosed with asthma, “exercise-induced asthma” or exercise-induced bronchoconstriction based on their symptoms, but this strategy regularly leads to misdiagnosis and improper patient management. Dyspnoea during exercise can ultimately be caused by numerous respiratory and nonrespiratory conditions, ranging from nonpathological to potentially fatal in severity. As, such it is important for healthcare providers to be familiar with the many factors that can cause dyspnoea during exercise in seemingly otherwise-healthy individuals and have a general understanding of the clinical approach to this patient population. This article reviews common conditions that ultimately cause athletes to report dyspnoea and associated symptoms, and provides insight for developing an efficient diagnostic plan. PMID:27408644

Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity.

PubMed

Chen, Shasha; Cai, Chenxu; Li, Zehua; Liu, Guangao; Wang, Yuande; Blonska, Marzenna; Li, Dan; Du, Juan; Lin, Xin; Yang, Meixiang; Dong, Zhongjun

2017-02-01

Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (T FH ) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in T FH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient T FH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. © 2017 Chen et al.

Dissection of SAP-dependent and SAP-independent SLAM family signaling in NKT cell development and humoral immunity

PubMed Central

Cai, Chenxu; Liu, Guangao; Wang, Yuande; Du, Juan; Lin, Xin; Yang, Meixiang

2017-01-01

Signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) mutations in X-linked lymphoproliferative disease (XLP) lead to defective NKT cell development and impaired humoral immunity. Because of the redundancy of SLAM family receptors (SFRs) and the complexity of SAP actions, how SFRs and SAP mediate these processes remains elusive. Here, we examined NKT cell development and humoral immunity in mice completely deficient in SFR. We found that SFR deficiency severely impaired NKT cell development. In contrast to SAP deficiency, SFR deficiency caused no apparent defect in follicular helper T (TFH) cell differentiation. Intriguingly, the deletion of SFRs completely rescued the severe defect in TFH cell generation caused by SAP deficiency, whereas SFR deletion had a minimal effect on the defective NKT cell development in SAP-deficient mice. These findings suggest that SAP-dependent activating SFR signaling is essential for NKT cell selection; however, SFR signaling is inhibitory in SAP-deficient TFH cells. Thus, our current study revises our understanding of the mechanisms underlying T cell defects in patients with XLP. PMID:28049627

Adverse weather conditions and fatal motor vehicle crashes in the United States, 1994-2012.

PubMed

Saha, Shubhayu; Schramm, Paul; Nolan, Amanda; Hess, Jeremy

2016-11-08

Motor vehicle crashes are a leading cause of injury mortality. Adverse weather and road conditions have the potential to affect the likelihood of motor vehicle fatalities through several pathways. However, there remains a dearth of assessments associating adverse weather conditions to fatal crashes in the United States. We assessed trends in motor vehicle fatalities associated with adverse weather and present spatial variation in fatality rates by state. We analyzed the Fatality Analysis Reporting System (FARS) datasets from 1994 to 2012 produced by the National Highway Traffic Safety Administration (NHTSA) that contains reported weather information for each fatal crash. For each year, we estimated the fatal crashes that were associated with adverse weather conditions. We stratified these fatalities by months to examine seasonal patterns. We calculated state-specific rates using annual vehicle miles traveled data for all fatalities and for those related to adverse weather to examine spatial variations in fatality rates. To investigate the role of adverse weather as an independent risk factor for fatal crashes, we calculated odds ratios for known risk factors (e.g., alcohol and drug use, no restraint use, poor driving records, poor light conditions, highway driving) to be reported along with adverse weather. Total and adverse weather-related fatalities decreased over 1994-2012. Adverse weather-related fatalities constituted about 16 % of total fatalities on average over the study period. On average, 65 % of adverse weather-related fatalities happened between November and April, with rain/wet conditions more frequently reported than snow/icy conditions. The spatial distribution of fatalities associated with adverse weather by state was different than the distribution of total fatalities. Involvement of alcohol or drugs, no restraint use, and speeding were less likely to co-occur with fatalities during adverse weather conditions. While adverse weather is reported for a large number of motor vehicle fatalities for the US, the type of adverse weather and the rate of associated fatality vary geographically. These fatalities may be addressed and potentially prevented by modifying speed limits during inclement weather, improving road surfacing, ice and snow removal, and providing transit alternatives, but the impact of potential interventions requires further research.

New arenavirus isolated in Brazil

PubMed Central

Coimbra, Terezinha Lisieux M; Nassar, Elza S; Burattini, Marcelo N; de Souza, Luiza Terezinha Madia; Ferreira, Ivani B; Rocco, Iray M; Travassos da Rosa, Amelia P A; Vasconcelos, Pedro F C; Pinheiro, Francisco P; LeDuc, James W; Rico-Hesse, Rebeca; Gonzalez, Jean-Paul; Jahrling, Peter B

2012-01-01

A new arenavirus, called Sabiá, was isolated in Brazil from a fatal case of haemorrhagic fever initially thought to be yellow fever. Antigenic and molecular characterisation indicated that Sabiá virus is a new member of the Tacaribe complex. A laboratory technician working with the agent was also infected and developed a prolonged, non-fatal influenza-like illness. Sabiá virus is yet another arenavirus causing human disease in South America. PMID:7905555

Development of a Comprehensive Neck Injury Criterion for Aircraft-Related Incidences

DTIC Science & Technology

1995-02-15

flight into ground because of distraction in cockpit. No attempt to eject, multiple extreme injuries. 38B 2 Multiple extreme FATAL; FATAL A-37B. Pilot...hypesthesia and hypalesthesia to the level of the lesion. (Reference 26) Pillar fracture A vertical fracture of the articular pillar (mass) resulting...from an Extension impaction of the involved mass by the ipsilateral superior (Hyperextension) articular mass during hyperextension and rotation. with

Fatal traumatic brain injury in older adults in Austria 1980-2012: an analysis of 33 years.

PubMed

Brazinova, Alexandra; Mauritz, Walter; Majdan, Marek; Rehorcikova, Veronika; Leitgeb, Johannes

2015-05-01

traumatic brain injury (TBI) is a significant public health problem. Developed countries report a significant increase of TBI in older adults in the past decades. The objective of this study was to investigate the changes in TBI-related mortality in older Austrians (65 years or older) between 1980 and 2012 (33 years) and to identify possible causes for these changes. data from Statistics Austria on mortality in Austria between 1980 and 2012 were screened and data on TBI-related mortality in adults aged 65 and older were extracted and analysed, based on the diagnostic codes of the International Classification of Diseases, 10th and 9th revision. Mortality rates were calculated for 5-year age groups; standardized mortality rates were calculated for the total. Mechanism of injury was analysed for all events, both sexes and individual age groups. between 1980 and 2012, 16,204 people aged 65 or older died from TBI in Austria; 61% of these were male. Fatal TBI cases and mortality rates increased in the oldest age groups (80 years or older). Half of the fatal TBI cases were caused by falls, 22% by traffic accidents and 17% by suicides. Rate of fall-related fatal TBI increased and rate of traffic accident-related fatal TBI decreased with age. preventive measures introduced in the past decades in the developed countries have contributed to a decrease in traffic injuries. However, falls in the older population are on the rise, mainly due to ageing of the population, throughout the reported period. It is important to take preventive measures to stop the epidemics of fall-related TBIs and fatalities in older adults. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Patterns of hospital transfer for self-poisoned patients in rural Sri Lanka: implications for estimating the incidence of self-poisoning in the developing world.

PubMed Central

Eddleston, Michael; Sudarshan, K.; Senthilkumaran, M.; Reginald, K.; Karalliedde, Lakshman; Senarathna, Lalith; de Silva, Dhammika; Rezvi Sheriff, M. H.; Buckley, Nick A.; Gunnell, David

2006-01-01

OBJECTIVES: Most data on self-poisoning in rural Asia have come from secondary hospitals. We aimed to: assess how transfers from primary to secondary hospitals affected estimates of case-fatality ratio (CFR); determine whether there was referral bias according to gender or poison; and estimate the annual incidence of all self-poisoning, and of fatal self-poisoning, in a rural developing-world setting. METHODS: Self-poisoning patients admitted to Anuradhapura General Hospital, Sri Lanka, were reviewed on admission from 1 July to 31 December 2002. We audited medical notes of self-poisoning patients admitted to 17 of the 34 surrounding peripheral hospitals for the same period. FINDINGS: A total of 742 patients were admitted with self-poisoning to the secondary hospital; 81 died (CFR 10.9%). 483 patients were admitted to 17 surrounding peripheral hospitals. Six patients (1.2%) died in peripheral hospitals, 249 were discharged home, and 228 were transferred to the secondary hospital. There was no effect of gender or age on likelihood of transfer; however, patients who had ingested oleander or paraquat were more likely to be transferred than were patients who had taken organophosphorus pesticides or other poisons. Estimated annual incidences of self-poisoning and fatal self-poisoning were 363 and 27 per 100,000 population, respectively, with an overall CFR of 7.4% (95% confidence interval 6.0-9.0). CONCLUSION: Fifty per cent of patients admitted to peripheral hospitals were discharged home, showing that CFRs based on secondary hospital data are inflated. However, while incidence of self-poisoning is similar to that in England, fatal self-poisoning is three times more common in Sri Lanka than fatal self-harm by all methods in England. Population based data are essential for making international comparisons of case fatality and incidence, and for assessing public health interventions. PMID:16628300

Evaluation of injury and fatality risk in rock and ice climbing.

PubMed

Schöffl, Volker; Morrison, Audry; Schwarz, Ulrich; Schöffl, Isabelle; Küpper, Thomas

2010-08-01

Rock and ice climbing are widely considered to be 'high-risk' sporting activities that are associated with a high incidence of severe injury and even death, compared with more mainstream sports. However, objective scientific data to support this perception are questionable. Accordingly, >400 sport-specific injury studies were analysed and compared by quantifying the injury incidence and objectively grading the injury severity (using the National Advisory Committee for Aeronautics score) per 1000 hours of sporting participation. Fatalities were also analysed. The analysis revealed that fatalities occurred in all sports, but it was not always clear whether the sport itself or pre-existing health conditions contributed or caused the deaths. Bouldering (ropeless climbing to low heights), sport climbing (mostly bolt protected lead climbing with little objective danger) and indoor climbing (climbing indoors on artificial rock structures), showed a small injury rate, minor injury severity and few fatalities. As more objective/external dangers exist for alpine and ice climbing, the injury rate, injury severity and fatality were all higher. Overall, climbing sports had a lower injury incidence and severity score than many popular sports, including basketball, sailing or soccer; indoor climbing ranked the lowest in terms of injuries of all sports assessed. Nevertheless, a fatality risk remains, especially in alpine and ice climbing. In the absence of a standard definition for a 'high-risk' sport, categorizing climbing as a high-risk sport was found to be either subjective or dependent on the definition used. In conclusion, this analysis showed that retrospective data on sport-specific injuries and fatalities are not reported in a standardized manner. To improve preventative injury measures for climbing sports, it is recommended that a standardized, robust and comprehensive sport-specific scoring model should be developed to report and fully evaluate the injury risk, severity of injuries and fatality risk in climbing sports.

GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran

PubMed Central

Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M

2015-01-01

Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor’s Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the car accidents, which were in their nature preventable, the key players in road safety including governments, car manufacturers, and road developers were recommended to use GIS based accident data for a more efficient planning and budgeting towards the intercity car accidents reduction. PMID:28255402

GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran.

PubMed

Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M

2015-01-01

Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor's Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the car accidents, which were in their nature preventable, the key players in road safety including governments, car manufacturers, and road developers were recommended to use GIS based accident data for a more efficient planning and budgeting towards the intercity car accidents reduction.

Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain

PubMed Central

Bastian, Thomas W.; Santarriaga, Stephanie; Nguyen, Thu An; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.

2015-01-01

Objectives Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling. In mice, chronic hypoxia induces a compensatory increase in brain blood vessel outgrowth. We hypothesized that developmental anemia, due to iron or copper deficiencies, induces angiogenesis/vasculogenesis in the neonatal brain. Methods To test our hypothesis, three independent experiments were performed where pregnant rats were fed iron- or copper-deficient diets from gestational day 2 through mid-lactation. Effects on the neonatal brain vasculature were determined using qPCR to assess mRNA levels of angiogenesis/vasculogenesis-associated genes and GLUT1 immunohistochemistry (IHC) to assess brain blood vessel density and complexity. Results Iron deficiency, but not copper deficiency, increased mRNA expression of brain endothelial cell- and angiogenesis/vasculogenesis-associated genes (i.e. Glut1, Vwf, Vegfa, Ang2, Cxcl12, and Flk1) in the neonatal brain, suggesting increased cerebrovascular density. Iron deficiency also increased hippocampal and cerebral cortical blood vessel branching by 62% and 78%, respectively. Discussion This study demonstrates increased blood vessel complexity in the neonatal iron-deficient brain, which is likely due to elevated angiogenic/vasculogenic signaling. At least initially, this is probably an adaptive response to maintain metabolic substrate homeostasis in the developing iron-deficient brain. However, this may also contribute to long-term neurodevelopmental deficits. PMID:26177275

The strength of graduated drivers license programs and fatalities among teen drivers and passengers.

PubMed

Morrisey, Michael A; Grabowski, David C; Dee, Thomas S; Campbell, Christine

2006-01-01

The purpose of this study is to investigate the effects of differentially stringent graduated drivers license programs on teen driver fatalities, day-time and night-time teen driver fatalities, fatalities of teen drivers with passengers present, and fatalities among teen passengers. The study uses 1992-2002 data on motor vehicle fatalities among 15-17-year-old drivers from the Fatality Analysis Reporting System to identify the effects of "good", "fair", and "marginal" GDL programs based upon designations by the Insurance Institute for Highway Safety. Analysis is conducted using conditional negative binomial regressions with fixed effects. "Good" programs reduce total fatalities among young drivers by 19.4% (c.i. -33.0%, -5.9%). "Fair" programs reduce night-time young driver fatalities by 12.6% (c.i. -23.9%, -1.2%), but have no effect on day-time fatalities. "Marginal" programs had no statistically meaningful effect on driver fatalities. All three types of programs reduced teen passenger fatalities, but the effects of limitations on the number of passengers appear to have had only minimal effects in reducing fatalities among young drivers themselves. Stronger GDL programs are more effective than weaker programs in reducing teenage motor vehicle fatalities.

The use of technology to address patterns of risk among teenage drivers.

PubMed

Brovold, Shawn; Ward, Nic; Donath, Max; Simon, Stephen; Shankwitz, Craig; Creaser, Janet

2007-01-01

The crash risk of teens is high, with fatal crash rates of teen drivers higher than any other age group. New approaches to reduce teen traffic fatalities are clearly needed. A possible approach to reduce the incidence of teen driver crashes and fatalities is through the use of vehicle-based intelligent driver support systems. To be most effective, the system should address the behaviors associated with an overwhelming number of teen fatal crashes: speed, low seatbelt use, and alcohol impairment. In-vehicle technology also offers an opportunity to address the issue of inexperience through enforcement of certain Graduated Driver's License provisions. To fully understand the capability of such technologies, there should be a concerted effort to further their development, and human factors testing should take place to understand their effects on the driver. If successfully implemented, a Teen Driver Support System (TDSS), such as the one described here, could significantly decrease the number of teens killed in traffic crashes.

Economic and cultural correlates of road-traffic accident fatality rates in OECD countries.

PubMed

Gaygisiz, Esma

2009-10-01

The relationships between economic conditions, cultural characteristics, personality dimensions, intelligence scores, and road-traffic accident mortality rates were investigated in 30 member and five accession countries of the Organisation for Economic Co-operation and Development (OECD). Economic indicators included the Gross Domestic Product (GDP) per capita, the unemployment rate, and the Gini index. Cultural variables included five Hofstede's cultural dimensions, seven Schwartz cultural value dimensions, NEO-PI-R scales, and the intelligence quotient (IQ). The results showed positive associations between favorable economic conditions (high income per capita, high employment rate, and low income inequality) and high traffic safety. Countries with higher road-traffic accident fatality rates were characterized by higher power distance and uncertainty avoidance as well as embeddedness and emphasis on social hierarchy. Countries with lower road-traffic accident fatality rates were more individualistic, egalitarian, and emphasized autonomy of individuals. Conscientiousness (from NEO-PI-R) and IQ correlated negatively with road-traffic accident fatalities.

Prominent barriers and motivators to installing ROPS: an analysis of survey responses from Pennsylvania and Vermont.

PubMed

Jenkins, P L; Sorensen, J A; Yoder, A; Myers, M; Murphy, D; Cook, G; Wright, F; Bayes, B; May, J J

2012-04-01

Tractor overturns contribute significantly to the number of work-related deaths that occur every year on U.S. farms. Although the agriculture, forestry, and fishing industries have the highest fatality rates of any industries, researchers predict that the elimination of tractor overturn fatalities could result in a noticeable reduction in the farm fatality rate. Rollover protection structures (ROPS) are 99% effective in preventing overturn fatalities. However, roughly 50% of U.S. tractors do not have a ROPS. In order to identify prominent barriers and motivators to installing ROPS, a phone survey was conducted with a random sample of farmers (n = 327) in Vermont and Pennsylvania, two states interested in developing ROPS installation programs. Results indicated that cost and perceived need were the most frequently highly rated barriers to ROPS installation in both states, while working near hills or ditches and concerns regarding liability were the most frequently highly rated motivators for installing ROPS. Additionally, older farmers identified limited use of a tractor as a highly rated barrier.

Non-fatal self-poisoning across age groups, in Sri Lanka.

PubMed

Rajapakse, Thilini; Christensen, Helen; Cotton, Sue; Griffiths, Kathleen Margaret

2016-02-01

Attempted or non-fatal self-poisoning in common in Sri Lanka, but little is known about variation of psychiatric morbidity and suicidal intent across differing ages. The aim of this study was to investigate factors associated with non-fatal self-poisoning in Sri Lanka across three different age groups (namely 14-24 years, 25-34 years and ≥ 35 years). It was anticipated that the findings of the study would inform and guide development of preventive interventions for non-fatal self-poisoning in this country. 935 participants were interviewed within one week of admission to hospital for medical management of non-fatal self-poisoning, over a consecutive 14-month period. Socio-demographic factors, types of poison ingested, triggers and psychiatric morbidity was examined as a function of age. Results showed that a majority (83%) of participants were aged below 35 years. Younger participants aged <25 years were significantly more likely to ingest medicinal overdoses, compared to older persons (aged 25-34 years, and ≥ 35 years), who were more likely to ingest pesticides. Recent interpersonal conflict was a proximal trigger seen in all age groups, but suicidal intent, depression and alcohol use disorders increased with age. The overall study findings indicate that most who carry out acts of non-fatal self-poisoning in Sri Lanka are young (aged <35 years). Interpersonal conflict as a trigger is common to all age groups, but psychiatric morbidity and suicidal intent is higher in the older age groups, as is pesticide ingestion. Age specific interventions may be efficacious in the prevention of non-fatal self-poisoning in Sri Lanka. Copyright © 2016 Elsevier B.V. All rights reserved.

Reported traumatic injuries among West Coast Dungeness crab fishermen, 2002–2014

PubMed Central

Case, Samantha; Bovbjerg, Viktor; Lucas, Devin; Syron, Laura; Kincl, Laurel

2015-01-01

Background Commercial fishing is a high-risk occupation. The West Coast Dungeness crab fishery has a high fatality rate; however, nonfatal injuries have not been previously studied. The purpose of this report was to describe the characteristics of fatal and nonfatal traumatic occupational injuries and associated hazards in this fleet during 2002–2014. Materials and methods Data on fatal injuries were obtained from a surveillance system managed by the National Institute for Occupational Safety and Health. Data on nonfatal injuries were manually abstracted from Coast Guard investigation reports and entered into a study database. Descriptive statistics were used to characterise demographics, injury characteristics, and work processes performed. Results Twenty-eight fatal and 45 nonfatal injuries were reported between 2002 and 2014 in the Dungeness crab fleet. Most fatalities were due to vessel disasters, and many nonfatal injuries occurred on-deck when fishermen were working with gear, particularly when hauling the gear (47%). The most frequently reported injuries affected the upper extremities (48%), and fractures were the most commonly reported injury type (40%). The overall fatality rate during this time period was 209 per 100,000 full-time equivalent workers and the rate of nonfatal injury was 3.4 per 1,000 full-time equivalent workers. Conclusions Dungeness crab fishermen are at relatively high risk for fatal injuries. Nonfatal injuries were limited to reported information, which hampers efforts to accurately estimate nonfatal injury risk and understand fishing hazards. Further research is needed to identify work tasks and other hazards that cause nonfatal injuries in this fleet. Engaging fishermen directly may help develop approaches for injury prevention. PMID:26726891

Injuries and fatalities among emergency medical technicians and paramedics in the United States.

PubMed

Maguire, Brian J; Smith, Sean

2013-08-01

Emergency medical services personnel treat 22 million patients a year, yet little is known of their risk of injury and fatality. Work-related injury and fatality rates among US paramedics and emergency medical technicians (EMTs) are higher than the national average for all occupations. Data collected by the Department of Labor (DOL) Bureau of Labor Statistics were reviewed to identify injuries and fatalities among EMTs and paramedics from 2003 through 2007. The characteristics of fatal injuries are described and the rates and relative risks of the non-fatal injuries were calculated and compared to the national average. Of the 21,749 reported cases, 21,690 involved non-fatal injuries or illnesses that resulted in lost work days among EMTs and paramedics within the private sector. Of the injuries, 3,710 (17%) resulted in ≥31 days of lost work time. A total of 14,470 cases (67%) involved sprains or strains; back injury was reported in 9,290 of the cases (43%); and the patient was listed as the source of injury in 7,960 (37%) cases. The most common events were overexertion (12,146, 56%), falls (2,169, 10%), and transportation-related (1,940, 9%). A total of 530 assaults were reported during the study period. Forty-five percent of the cases occurred among females (females accounted for 27% of employment in this occupation during 2007). In 2007, EMTs and paramedics suffered 349.9 injuries with days away from work per 10,000 full-time workers, compared to an average of 122.2 for all private industry occupations (Relative risk = 2.9; 95% CI: 2.7-3.0). During the study period, 59 fatalities occurred among EMTs and paramedics in both the private industry and in the public sector. Of those fatalities, 51 (86%) were transportation-related and five (8%) were assaults; 33 (56%) were classified as "multiple traumatic injuries." Data from the DOL show that EMTs and paramedics have a rate of injury that is about three times the national average for all occupations. The vast majority of fatalities are secondary to transportation related-incidents. Assaults are also identified as a significant cause of fatality. The findings also indicate that females in this occupational group may have a disproportionately larger number of injuries. Support is recommended for further research related to causal factors and for the development, evaluation and promulgation of evidence-based interventions to mitigate this problem.

Spatial Analysis of Earthquake Fatalities in the Middle East, 1970-2008: First Results

NASA Astrophysics Data System (ADS)

Khaleghy Rad, M.; Evans, S. G.; Brenning, A.

2010-12-01

Earthquakes claim the lives of thousands of people each year and the annual number of earthquake fatalities in the Middle East (21 countries) is 20 % of the total yearly fatalities of the World. There have been several attempts to estimate the number of fatalities in a given earthquake. We review the results of previous attempts and present an estimation of fatalities using a new conceptual model for life loss that includes hazard (earthquake magnitude and focal depth), vulnerability (GDP value of countries and elapsed time since 1970 as proxy variables) and exposed population in the affected area of a given earthquake. PAGER_CAT is a global catalog (http://earthquake.usgs.gov/research/data/pager/) that presents information on casualties of earthquakes since 1900. Although, the catalog itself is almost a complete record of fatal earthquakes, the data on number of deaths is not complete. We use PAGER_CAT to assemble a Middle East (the latitude and longitude of 10°-42° N and 24°-64° E respectively) catalog for the period 1970-2008 that includes 202 events with published number of fatalities, including events with zero casualties. We investigated the effect of components of each event, e.g. exposed population, instrumental earthquake magnitude, focal depth, date (year of event) and GDP on earthquake fatalities in Middle East in the 202 events with detailed fatality estimates. To estimate the number of people exposed to each event, we used a fatality threshold for peak ground acceleration of 0.1g to calculate the radius of affected area. The exposed population of each event is the enclosed population of each circle calculated from gridded population data available on SEDAC (http://sedac.ciesin.columbia.edu/gpw/global.jsp) using ArcGIS. Results of our statistical model, using Poisson regression in R statistical software, show that the number of fatalities due to earthquakes is in direct (positive) relation to the exposed population and the magnitude of the earthquake at the epicenter. On the other hand, it is in inverse (negative) relation to elapsed time since 1970, focal depth and GDP of the country affected. These spatial and temporal patterns of life loss are consistent with the patterns expected within our conceptual framework in relationship with hazard, exposed population and proxies of vulnerability. Our findings suggest that for earthquakes with comparable physical characteristics, the number of fatalities has been falling since 1970 in the Middle East region. We interpret this as an overall reduction of vulnerability of the Middle East during 1970-2008. Ongoing research is focusing on more detailed analysis of particular indicators of vulnerability reduction such as the development of earthquake building codes and preparedness, and on the spatial disaggregation of exposed population and the attenuation of earthquake magnitude.

The iron status at birth of neonates with risk factors for developing iron deficiency: a pilot study

PubMed Central

MacQueen, BC; Christensen, RD; Ward, DM; Bennett, ST; O’Brien, EA; Sheffield, MJ; Baer, VL; Snow, GL; Lewis, KA Weaver; Fleming, RE; Kaplan, J

2016-01-01

OBJECTIVE Small-for-gestational-age (SGA) neonates, infants of diabetic mothers (IDM) and very-low-birth weight premature neonates (VLBW) are reported to have increased risk for developing iron deficiency and possibly associated neurocognitive delays. STUDY DESIGN We conducted a pilot study to assess iron status at birth in at-risk neonates by measuring iron parameters in umbilical cord blood from SGA, IDM, VLBW and comparison neonates. RESULTS Six of the 50 infants studied had biochemical evidence of iron deficiency at birth. Laboratory findings consistent with iron deficiency were found in one SGA, one IDM, three VLBW, and one comparison infant. None of the infants had evidence of iron deficiency anemia. CONCLUSIONS Evidence of biochemical iron deficiency at birth was found in 17% of screened neonates. Studies are needed to determine whether these infants are at risk for developing iron-limited erythropoiesis, iron deficiency anemia or iron-deficient neurocognitive delay. PMID:27977019

Molecular mechanisms of cryptococcal meningitis

PubMed Central

Liu, Tong-Bao; Perlin, David; Xue, Chaoyang

2012-01-01

Fungal meningitis is a serious disease caused by a fungal infection of the central nervous system (CNS) mostly in individuals with immune system deficiencies. Fungal meningitis is often fatal without proper treatment, and the mortality rate remains unacceptably high even with antifungal drug interventions. Currently, cryptococcal meningitis is the most common fungal meningitis in HIV-1/AIDS, and its disease mechanism has been extensively studied. The key steps for fungi to infect brain and cause meningitis after establishment of local infection are the dissemination of fungal cells to the bloodstream and invasion through the blood brain barrier to reach the CNS. In this review, we use cryptococcal CNS infection as an example to describe the current molecular understanding of fungal meningitis, including the establishment of the infection, dissemination, and brain invasion. Host and microbial factors that contribute to these infection steps are also discussed. PMID:22460646

Ethylene and nitric oxide interact to regulate the magnesium deficiency-induced root hair development in Arabidopsis.

PubMed

Liu, Miao; Liu, Xing Xing; He, Xiao Lin; Liu, Li Juan; Wu, Hao; Tang, Cai Xian; Zhang, Yong Song; Jin, Chong Wei

2017-02-01

Nitric oxide (NO) and ethylene respond to biotic and abiotic stresses through either similar or independent processes. This study examines the mechanism underlying the effects of NO and ethylene on promoting root hair development in Arabidopsis under magnesium (Mg) deficiency. The interaction between NO and ethylene in the regulation of Mg deficiency-induced root hair development was investigated using NO- and ethylene-related mutants and pharmacological methods. Mg deficiency triggered a burst of NO and ethylene, accompanied by a stimulated development of root hairs. Interestingly, ethylene facilitated NO generation by activation of both nitrate reductase and nitric oxide synthase-like (NOS-L) in the roots of Mg-deficient plants. In turn, NO enhanced ethylene synthesis through stimulating the activities of 1-aminocyclopropane-1-carboxylate (ACC) oxidase and ACC synthase (ACS). These two processes constituted an NO-ethylene feedback loop. Blocking either of these two processes inhibited the stimulation of root hair development under Mg deficiency. In conclusion, we suggest that Mg deficiency increases the production of NO and ethylene in roots, each influencing the accumulation and role of the other, and thus these two signals interactively regulate Mg deficiency-induced root hair morphogenesis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Distance matters: Effect of geographic trauma system resource organization on fatal motor vehicle collisions.

PubMed

Brown, Joshua B; Rosengart, Matthew R; Billiar, Timothy R; Peitzman, Andrew B; Sperry, Jason L

2017-07-01

Trauma systems improve outcome; however, it is unclear how geographic organization of trauma system resources (TSR) affects outcome. Our objective was to evaluate the relationship of fatal motor vehicle collision (MVC) rates and the distance from individual MVC locations to the nearest TSR as a measure of the geographical organization of trauma systems, as well as how theoretical changes in the distribution of TSR may affect fatal MVC rates. All fatal MVC in Pennsylvania 2013-2014 were mapped from the Fatality Analysis Reporting System database. Deaths on scene were excluded. TSR including trauma centers and helicopter bases were mapped. Distance between each fatal MVC and nearest TSR was calculated. The primary outcome was fatal MVC rate per 100 million vehicle miles traveled (VMT). Empiric Bayes kriging and hot spot analysis were performed to evaluate geographic patterns in fatal MVC rates. Association between fatal MVC rate and distance to the nearest TSR was evaluated with linear regression. Spatial lag regression evaluated this association while controlling for MVC and county-level characteristics. We identified 886 fatalities from 863 fatal MVC. Median fatal MVC rate was 0.187 per 100 million VMT. Higher fatal MVC rates and fatality hot spots occur in locations farther from TSR. The fatal MVC rate increased 0.141 per 100 million VMT for every 10 miles farther from the nearest TSR (p < 0.01). When controlling for confounders, the fatal MVC rate increased by 0.089 per 100 million VMT for every 10 miles farther from the nearest TSR (p < 0.01). If two helicopters stationed at trauma centers were relocated into the highest fatality regions, our model predicts a 12.3% relative reduction in the overall MVC fatality rate. Increasing distance to the nearest TSR is associated with increasing fatal MVC rate. The geographic organization of trauma systems may impact outcome, and geospatial analysis can allow data-driven changes to potentially improve outcome. Prognostic/Epidemiologic, level III; Case management, level III.

Fatalities and fatality rates in alcohol-impaired crashes by state, 2005-2006

DOT National Transportation Integrated Search

2008-02-01

In 2006, as compared to 2005, while the overall fatality rate declined from 1.46 to 1.41 fatalities per 100 million vehicle miles of travel (VMT), the alcohol-impaired fatality rate remained flat at 0.45 fatalities per 100 million VMT. In 2006, the a...

Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

PubMed

Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-05-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.

Fatal injuries among urban children in South Africa: risk distribution and potential for reduction

PubMed Central

van Niekerk, Ashley; Laflamme, Lucie

2010-01-01

Abstract Objective To determine the leading causes of fatal injury for urban South African children aged 0–14 years, the distribution of those causes and the current potential for safety improvements. Methods We obtained injury surveillance data from the National Injury Mortality Surveillance System 2001–2003 for six major South African cities varying in size, development and sociodemographic composition. We calculated age-adjusted rates, by sex, population group and city, for death from the five leading causes of fatal injury as well as population attributable risks (PARs). Findings The leading causes of fatal injury in childhood included road traffic injuries – among vehicle passengers and especially among pedestrians – drowning, burns and, in some cities, firearm injuries. Large differences in PARs were observed, particularly for population groups and cities. Disparities between cities and between population groups were largest for deaths from pedestrian injuries, while differences between boys and girls were greatest for drowning deaths. Conclusion In the face of the high variability observed between cities and population groups in the rates of the most common types of fatal injuries, a safety agenda should combine safety-for-all countermeasures – i.e. lowering injury rates for all – and targeted countermeasures that help reduce the burden for those at greatest risk. PMID:20431790

Pulmonary and central nervous system pathology in fatal cases of hand foot and mouth disease caused by enterovirus A71 infection.

PubMed

Wang, Zijun; Nicholls, John M; Liu, Fengfeng; Wang, Joshua; Feng, Zijian; Liu, Dongge; Sun, Yanni; Zhou, Cheng; Li, Yunqian; Li, Hai; Qi, Shunxiang; Huang, Xueyong; Sui, Jilin; Liao, Qiaohong; Peiris, Malik; Yu, Hongjie; Wang, Yu

2016-04-01

In the past 17 years, neurological disease associated with enterovirus A71 (EV-A71) has increased dramatically in the Asia-Pacific region with a high fatality rate in young infants, often due to pulmonary oedema, however the mechanism of this oedema remains obscure. We analysed the brainstem, heart and lungs of 15 fatal cases of confirmed EV-A71 infection in order to understand the pathophysiological mechanism of death and pulmonary oedema. In keeping with other case studies, the main cause of death was neurogenic pulmonary oedema. In the brainstem, 11 cases showed inflammation and all cases showed parenchymal inflammation with seven cases showing moderate or severe clasmatodendrosis. No viral antigen was detected in sections of the brainstem in any of the cases. All fatal cases showed evidence of pulmonary oedema; however, there was absence of direct pulmonary viral damage or myocarditis-induced damage and EV-A71 viral antigen staining was negative. Though there was no increase in staining for Na/K-ATPase, 11 of the 15 cases showed a marked reduction in aquaporin-4 staining in the lung, and this reduction may contribute to the development of fatal pulmonary oedema. Copyright © 2016. Published by Elsevier B.V.

Maternal Iron Deficiency Anemia as a Risk Factor for the Development of Retinopathy of Prematurity.

PubMed

Dai, Alper I; Demiryürek, Seniz; Aksoy, Sefika Nur; Perk, Peren; Saygili, Oguzhan; Güngör, Kivanc

2015-08-01

Retinopathy of prematurity is a proliferative vascular disease affecting premature newborns and occurs during vessel development and maturation. The aim of this study was to evaluate the maternal iron deficiency anemia as possible risk factors associated with the development of retinopathy of prematurity among premature or very low birth weight infants. In this study, mothers of 254 infants with retinopathy of prematurity were analyzed retrospectively, and their laboratory results of medical records during pregnancy were reviewed for possible iron deficiency anemia. In a cohort of 254 mothers of premature infants with retinopathy of prematurity, 187 (73.6%) had iron deficiency, while the remaining 67 (26.4%) mothers had no deficiency. Babies born to mothers with iron deficiency anemia with markedly decreased hemoglobin, hematocrit, mean corpuscular volume, serum iron, and ferritin levels were more likely to develop retinopathy of prematurity. Our results are the first to suggest that maternal iron deficiency is a risk factor for the development of retinopathy of prematurity. Our data suggest that maternal iron supplementation therapy during pregnancy might lower the risk of retinopathy of prematurity. Copyright © 2015 Elsevier Inc. All rights reserved.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

PubMed

Alcántara-Alonso, Viridiana; Alvarez-Salas, Elena; Matamoros-Trejo, Gilberto; de Gortari, Patricia

2017-10-18

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Thiamin deficiency on fetal brain development with and without prenatal alcohol exposure.

PubMed

Kloss, Olena; Eskin, N A Michael; Suh, Miyoung

2018-04-01

Adequate thiamin levels are crucial for optimal health through maintenance of homeostasis and viability of metabolic enzymes, which require thiamine as a co-factor. Thiamin deficiency occurs during pregnancy when the dietary intake is inadequate or excessive alcohol is consumed. Thiamin deficiency leads to brain dysfunction because thiamin is involved in the synthesis of myelin and neurotransmitters (e.g., acetylcholine, γ-aminobutyric acid, glutamate), and its deficiency increases oxidative stress by decreasing the production of reducing agents. Thiamin deficiency also leads to neural membrane dysfunction, because thiamin is a structural component of mitochondrial and synaptosomal membranes. Similarly, in-utero exposure to alcohol leads to fetal brain dysfunction, resulting in negative effects such as fetal alcohol spectrum disorder (FASD). Thiamin deficiency and prenatal exposure to alcohol could act synergistically to produce negative effects on fetal development; however, this area of research is currently under-studied. This minireview summarizes the evidence for the potential role of thiamin deficiency in fetal brain development, with or without prenatal exposure to alcohol. Such evidence may influence the development of new nutritional strategies for preventing or mitigating the symptoms of FASD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brautigam, Chad A.; Chuang, Jacinta L.; Tomchick, Diana R.

Human dihydrolipoamide dehydrogenase (hE3) is an enzymatic component common to the mitochondrial {alpha}-ketoacid dehydrogenase and glycine decarboxylase complexes. Mutations to this homodimeric flavoprotein cause the often-fatal human disease known as E3 deficiency. To catalyze the oxidation of dihydrolipoamide, hE3 uses two molecules: noncovalently bound FAD and a transiently bound substrate, NAD{sup +}. To address the catalytic mechanism of hE3 and the structural basis for E3 deficiency, the crystal structures of hE3 in the presence of NAD{sup +} or NADH have been determined at resolutions of 2.5 {angstrom} and 2.1 {angstrom}, respectively. Although the overall fold of the enzyme is similarmore » to that of yeast E3, these two structures differ at two loops that protrude from the proteins and at their FAD-binding sites. The structure of oxidized hE3 with NAD{sup +} bound demonstrates that the nicotinamide moiety is not proximal to the FAD. When NADH is present, however, the nicotinamide base stacks directly on the isoalloxazine ring system of the FAD. This is the first time that this mechanistically requisite conformation of NAD{sup +} or NADH has been observed in E3 from any species. Because E3 structures were previously available only from unicellular organisms, speculations regarding the molecular mechanisms of E3 deficiency were based on homology models. The current hE3 structures show directly that the disease-causing mutations occur at three locations in the human enzyme: the dimer interface, the active site, and the FAD and NAD{sup +}-binding sites. The mechanisms by which these mutations impede the function of hE3 are discussed.« less

Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.

PubMed

Horvath, Gabriella A; Davidson, A G F; Stockler-Ipsiroglu, Sylvia G; Lillquist, Yolanda P; Waters, Paula J; Olpin, S; Andresen, B S; Palaty, Jan; Nelson, Judie; Vallance, Hilary

2008-01-01

Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). Medium chain length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further. Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A > G MCAD mutation and three others were compound heterozygous for the c.985A > G and a second mutation. Two novel mutations were identified (c.260T > C and c.382T > A). The estimated incidence of MCAD was approximately 1:12,000 live births. Upon frequent feeding and carnitine supplementation, none of the patients had metabolic crises or adverse outcomes. Frequency of MCAD in BC is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD.

Chemokine Receptor Ccr7 Restricts Fatal West Nile Virus Encephalitis.

PubMed

Bardina, Susana V; Brown, Julia A; Michlmayr, Daniela; Hoffman, Kevin W; Sum, Janet; Pletnev, Alexander G; Lira, Sergio A; Lim, Jean K

2017-05-15

West Nile virus (WNV) is a mosquito-transmitted flavivirus that can cause debilitating encephalitis. To delineate the mechanisms behind this pathology, we studied Ccr7-deficient mice, which afforded us the capacity to study infection in mice with disrupted peripheral cellular trafficking events. The loss of Ccr7 resulted in an immediate pan-leukocytosis that remained elevated throughout the infection. This leukocytosis resulted in a significant enhancement of leukocyte accumulation within the central nervous system (CNS). Despite an excess of virus-specific T cells in the CNS, Ccr7-deficient mice had significantly higher CNS viral loads and mortality rates than wild-type animals. Mechanistically, the elevated trafficking of infected myeloid cells into the brain in Ccr7-deficient mice resulted in increased levels of WNV in the CNS, thereby effectively contributing to neuroinflammation and lowering viral clearance. Combined, our experiments suggest that during WNV infection, Ccr7 is a gatekeeper for nonspecific viral transference to the brain. IMPORTANCE In this study, we show that Ccr7 is required for the sufficient migration of dendritic cells and T cells into the draining lymph node immediately following infection and for the restriction of leukocyte migration into the brain. Further, the severe loss of dendritic cells in the draining lymph node had no impact on viral replication in this organ, suggesting that WNV may migrate from the skin into the lymph node through another mechanism. Most importantly, we found that the loss of Ccr7 results in a significant leukocytosis, leading to hypercellularity within the CNS, where monocytes/macrophages contribute to CNS viremia, neuroinflammation, and increased mortality. Together, our data point to Ccr7 as a critical host defense restriction factor limiting neuroinflammation during acute viral infection. Copyright © 2017 American Society for Microbiology.

Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis

PubMed Central

Peng, Xueyan; Moore, Meagan; Mathur, Aditi; Zhou, Yang; Sun, Huanxing; Gan, Ye; Herazo-Maya, Jose D.; Kaminski, Naftali; Hu, Xinyuan; Pan, Hongyi; Ryu, Changwan; Osafo-Addo, Awo; Homer, Robert J.; Feghali-Bostwick, Carol; Fares, Wassim H.; Gulati, Mridu; Hu, Buqu; Lee, Chun-Geun; Elias, Jack A.; Herzog, Erica L.

2016-01-01

Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations. Our findings reveal that relative to control participants, patients with idiopathic pulmonary fibrosis demonstrate excessive monocyte migration and underexpression of PLXNC1 in the lungs and circulation, a finding that is recapitulated in the setting of scleroderma-related interstitial lung disease. Relative to wild type, PLXNC1−/− mouse macrophages are excessively migratory, and PLXNC1−/− mice show exacerbated collagen accumulation in response to either inhaled bleomycin or inducible lung targeted TGF-β1 overexpression. These findings are ameliorated by replacement of PLXNC1 on bone marrow–derived cells or by genetic deletion of Syt7. These data demonstrate the previously unrecognized observation that PLXNC1 deficiency permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.—Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D., Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali-Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog, E. L. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. PMID:27609773

Characteristics of fatal abusive head trauma among children in the USA: 2003-2007: an application of the CDC operational case definition to national vital statistics data.

PubMed

Parks, Sharyn E; Kegler, Scott R; Annest, Joseph L; Mercy, James A

2012-06-01

In March of 2008, an expert panel was convened at the Centers for Disease Control and Prevention to develop code-based case definitions for abusive head trauma (AHT) in children under 5 years of age based on the International Classification of Diseases, 10th Revision (ICD-10) nature and cause of injury codes. This study presents the operational case definition and applies it to US death data. National Center for Health Statistics National Vital Statistics System data on multiple cause-of-death from 2003 to 2007 were examined. Inspection of records with at least one ICD-10 injury/disease code and at least one ICD-10 cause code from the AHT case definition resulted in the identification of 780 fatal AHT cases, with 699 classified as definite/presumptive AHT and 81 classified as probable AHT. The fatal AHT rate was highest among children age <1 year with a peak in incidence that occurred at 1-2 months of age. Fatal AHT incidence rates were higher for men than women and were higher for non-Hispanic African-Americans compared to other racial/ethnic groups. Fatal AHT incidence was relatively constant across seasons. This report demonstrates that the definition can help to identify population subgroups at higher risk for AHT defined by year and month of death, age, sex and race/ethnicity. This type of definition may be useful for various epidemiological applications including research and surveillance. These activities can in turn inform further development of prevention activities, including educating parents about the dangers of shaking and strategies for managing infant crying.

Opportunities for crash and injury reduction: A multiharm approach for crash data analysis.

PubMed

Mallory, Ann; Kender, Allison; Moorhouse, Kevin

2017-05-29

A multiharm approach for analyzing crash and injury data was developed for the ultimate purpose of getting a richer picture of motor vehicle crash outcomes for identifying research opportunities in crash safety. Methods were illustrated using a retrospective analysis of 69,597 occupant cases from NASS CDS from 2005 to 2015. Occupant cases were analyzed by frequency and severity of outcome: fatality, injury by Abbreviated Injury Scale (AIS), number of cases, attributable fatality, disability, and injury costs. Comparative analysis variables included precrash scenario, impact type, and injured body region. Crash and injury prevention opportunities vary depending on the search parameters. For example, occupants in rear-end crash scenarios were more frequent than in any other precrash configuration, yet there were significantly more fatalities and serious injury cases in control loss, road departure, and opposite direction crashes. Fatality is most frequently associated with head and thorax injury, and disability is primarily associated with extremity injury. Costs attributed to specific body regions are more evenly distributed, dominated by injuries to the head, thorax, and extremities but with contributions from all body regions. Though AIS 3+ can be used as a single measure of harm, an analysis based on multiple measures of harm gives a much more detailed picture of the risk presented by a particular injury or set of crash conditions. The developed methods represent a new approach to crash data mining that is expected to be useful for the identification of research priorities and opportunities for reduction of crashes and injuries. As the pace of crash safety improvement accelerates with innovations in both active and passive safety, these techniques for combining outcome measures for insights beyond fatality and serious injury will be increasingly valuable.

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice

PubMed Central

Yang, Hao; Wang, Shu Pei; Mitchell, Grant A.

2017-01-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency. PMID:29232702

Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

PubMed

Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

2017-12-01

Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

Revisiting the Role of the Urban Environment in Substance Use: The Case of Analgesic Overdose Fatalities

PubMed Central

Ransome, Yusuf; Keyes, Katherine M.; Koenen, Karestan C.; Tardiff, Kenneth; Vlahov, David; Galea, Sandro

2013-01-01

Objectives. We examined whether neighborhood social characteristics (income distribution and family fragmentation) and physical characteristics (clean sidewalks and dilapidated housing) were associated with the risk of fatalities caused by analgesic overdose. Methods. In a case-control study, we compared 447 unintentional analgesic opioid overdose fatalities (cases) with 3436 unintentional nonoverdose fatalities and 2530 heroin overdose fatalities (controls) occurring in 59 New York City neighborhoods between 2000 and 2006. Results. Analgesic overdose fatalities were less likely than nonoverdose unintentional fatalities to have occurred in higher-income neighborhoods (odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.70, 0.96) and more likely to have occurred in fragmented neighborhoods (OR = 1.35; 95% CI = 1.05, 1.72). They were more likely than heroin overdose fatalities to have occurred in higher-income (OR = 1.31; 95% CI = 1.12, 1.54) and less fragmented (OR = 0.71; 95% CI = 0.55, 0.92) neighborhoods. Conclusions. Analgesic overdose fatalities exhibit spatial patterns that are distinct from those of heroin and nonoverdose unintentional fatalities. Whereas analgesic fatalities typically occur in lower-income, more fragmented neighborhoods than nonoverdose fatalities, they tend to occur in higher-income, less unequal, and less fragmented neighborhoods than heroin fatalities. PMID:24134362

Development and characterization of a mouse with profound biotinidase deficiency: a biotin-responsive neurocutaneous disorder.

PubMed

Pindolia, Kirit; Jordan, Megan; Guo, Caiying; Matthews, Nell; Mock, Donald M; Strovel, Erin; Blitzer, Miriam; Wolf, Barry

2011-02-01

Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some symptoms, once they occur, such as developmental delay, hearing loss and optic atrophy, are usually irreversible. To prevent development of symptoms, the disorder is screened for in the newborn period in essentially all states and in many countries. In order to better understand many aspects of the pathophysiology of the disorder, we have developed a transgenic biotinidase-deficient mouse. The mouse has a null mutation that results in no detectable serum biotinidase activity or cross-reacting material to antibody prepared against biotinidase. When fed a biotin-deficient diet these mice develop neurological and cutaneous symptoms, carboxylase deficiency, mild hyperammonemia, and exhibit increased urinary excretion of 3-hydroxyisovaleric acid and biotin and biotin metabolites. The clinical features are reversed with biotin supplementation. This biotinidase-deficient animal can be used to study systematically many aspects of the disorder and the role of biotinidase, biotin and biocytin in normal and in enzyme-deficient states. Copyright © 2010 Elsevier Inc. All rights reserved.

Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

PubMed Central

Foong, Rachel E.; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

2014-01-01

Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron sections from formalin‐fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)‐β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D‐deficient and ‐replete fetal mice for quantification of ASM density and relative gene expression of TGF‐β signaling pathway molecules. Eight‐week‐old adult vitamin D‐deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D‐deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D‐deficient male and female mice had reduced TGF‐β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF‐β1 and TGF‐β receptor I was downregulated in vitamin D‐deficient female fetal mice. Decreased expression of TGF‐β1 and TGF‐β receptor I during early lung development in vitamin D‐deficient mice may contribute to airway remodeling and AHR in vitamin D‐deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease. PMID:24760528

Lack of MyD88 protects the immunodeficient host against fatal lung inflammation triggered by the opportunistic bacteria Burkholderia cenocepacia.

PubMed

Ventura, Grasiella M de C; Balloy, Viviane; Ramphal, Reuben; Khun, Huot; Huerre, Michel; Ryffel, Bernhard; Plotkowski, Maria-Cristina M; Chignard, Michel; Si-Tahar, Mustapha

2009-07-01

Burkholderia cenocepacia is an opportunistic pathogen of major concern for cystic fibrosis patients as well as immunocompromised cancer patients and transplant recipients. The mechanisms by which B. cenocepacia triggers a rapid health deterioration of the susceptible host have yet to be characterized. TLR and their key signaling intermediate MyD88 play a central role in the detection of microbial molecular patterns and in the initiation of an effective immune response. We performed a study to better understand the role of TLR-MyD88 signaling in B. cenocepacia-induced pathogenesis in the immunocompromised host, using an experimental murine model. The time-course of several dynamic parameters, including animal survival, bacterial load, and secretion of critical inflammatory mediators, was compared in infected and immunosuppressed wild-type and MyD88(-/-) mice. Notably, when compared with wild-type mice, infected MyD88(-/-) animals displayed significantly reduced levels of inflammatory mediators (including KC, TNF-alpha, IL-6, MIP-2, and G-CSF) in blood and lung airspaces. Moreover, despite a higher transient bacterial load in the lungs, immunosuppressed mice deficient in MyD88 had an unexpected survival advantage. Finally, we showed that this B. cenocepacia-induced life-threatening infection of wild-type mice involved the proinflammatory cytokine TNF-alpha and could be prevented by corticosteroids. Altogether, our findings demonstrate that a MyD88-dependent pathway can critically contribute to a detrimental host inflammatory response that leads to fatal pneumonia.

Iron deficiency and cognitive functions.

PubMed

Jáuregui-Lobera, Ignacio

2014-01-01

Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%-6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups.

Indiana crash facts 1999

DOT National Transportation Integrated Search

1997-01-01

The 892 fatal crashes in 1999 resulted in 1,021 fatalities. : This equates to a fatality each and every 8 hours : during 1999. The number of fatalities and fatal crashes : represented one of the worst years in the past decade for : Indiana. The 72,...

Germ Line IgM Is Sufficient, but Not Required, for Antibody-Mediated Alphavirus Clearance from the Central Nervous System.

PubMed

Nilaratanakul, Voraphoj; Chen, Jie; Tran, Oanh; Baxter, Victoria K; Troisi, Elizabeth M; Yeh, Jane X; Griffin, Diane E

2018-04-01

Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase-deficient (AID -/- ), secretory IgM-deficient (sIgM -/- ), and AID -/- sIgM -/- double-knockout (DKO) mice with those of wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses, and B cell infiltration into the CNS. Because AID is essential for immunoglobulin class switch recombination and somatic hypermutation, AID -/- mice produce only germ line IgM, while sIgM -/- mice secrete IgG but no IgM and DKO mice produce no secreted immunoglobulin. After intracerebral infection with the TE strain of SINV, most mice recovered. Development of neurologic disease occurred slightly later in sIgM -/- mice, but disease severity, weight loss, and survival were similar between the groups. AID -/- mice produced high levels of SINV-specific IgM, while sIgM -/- mice produced no IgM and high levels of IgG2a compared to WT mice. All mice cleared infectious virus from the spinal cord, but DKO mice failed to clear infectious virus from brain and had higher levels of viral RNA in the CNS late after infection. The numbers of infected cells and the amount of cell death in brain were comparable. We conclude that antibody is required and that either germ line IgM or IgG is sufficient for clearance of virus from the CNS. IMPORTANCE Mosquito-borne alphaviruses that infect neurons can cause fatal encephalomyelitis. Recovery requires a mechanism for the immune system to clear virus from infected neurons without harming the infected cells. Antiviral antibody has previously been shown to be a noncytolytic means for alphavirus clearance. Antibody-secreting cells enter the nervous system after infection and produce antiviral IgM before IgG. Clinical studies of human viral encephalomyelitis suggest that prompt production of IgM is associated with recovery, but it was not known whether IgM is effective for clearance. Our studies used mice deficient in production of IgM, IgG, or both to characterize the antibody necessary for alphavirus clearance. All mice developed similar signs of neurologic disease and recovered from infection. Antibody was necessary for virus clearance from the brain, and either early germ line IgM or IgG was sufficient. These studies support the clinical observation that prompt production of antiviral antibody is a determinant of outcome. Copyright © 2018 American Society for Microbiology.

Severe and fatal obstetric injury claims in relation to labor unit volume.

PubMed

Milland, Maria; Mikkelsen, Kim L; Christoffersen, Jens K; Hedegaard, Morten

2015-05-01

To assess possible association between the incidence of approved claims for severe and fatal obstetric injuries and delivery volume in Denmark. A nationwide panel study of labor units. Claimants seeking financial compensation due to injuries occurring in labor units in 1995-2012. Exposure information regarding the annual number of deliveries per labor unit was retrieved from the Danish National Birth Register. Outcome information was retrieved from the Danish Patient Compensation Association. Exposure was categorized in delivery volume quintiles as annual volume per labor unit: (10-1377), (1378-2016), (2017-2801), (2802-3861), (3862-6659). Five primary measures of outcome were used. Incidence rate ratios of (A) Submitted claims, (B) Approved claims, (C) Approved severe injury claims (120% degree of disability), (D) Approved fatal injury claims, and (C+D) Combined. 1 151 734 deliveries in 51 labor units and 1872 submitted claims were included. The incidence rate ratios of approved claims overall, of approved fatal injury claims, and of approved severe and fatal injuries combined increased significantly with decreasing annual delivery volume. Face value incidence rate ratios of approved severe injuries increased with decreasing labor unit volume, but the association did not reach statistical significance. High volume labor units appear associated with fewer approved and fewer fatal injury claims compared with units with less volume. The findings support the development towards consolidation of units in Denmark. A suggested option would be to tailor obstetric patient safety initiatives according to the delivery volume of individual labor units. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Disaster-related fatalities among US citizens traveling abroad.

PubMed

Partridge, Robert; Bouslough, David; Proano, Lawrence

2013-01-01

To describe the locations and risk of death associated with natural disaster fatalities for US citizens traveling abroad. A retrospective database review of US citizen disaster deaths occurring worldwide. None. Information on fatalities due to disasters was abstracted from the US Department of State Web site reporting deaths of US citizens abroad by non-natural causes from October 2002 through June 2012. The main outcome measures were the frequency of disaster deaths and countries where disasters occurred. Descriptive statistics and rates were used to evaluate the study data. There were 7,963 total non-natural deaths of US citizens traveling abroad during the study period. Of these, 163 (2.0 percent) were disaster-related deaths, involving 19 disaster events in 15 countries. Only two disaster-related events resulted in more than two deaths of US travelers-the 2010 earthquake in Haiti causing 121 fatalities (74.2 percent of disaster deaths), and the 2004 tsunami in Thailand causing 22 fatalities (13.5 percent of disaster deaths). The approximate annual mean death rate for US citizen travelers as a result of disaster events is 0.27 deaths/1 million travelers, compared with 1.4 deaths/1 million residents due to disaster annually within the United States. The risk of disaster-related fatality is low for US citizens traveling abroad. Although disaster-related death among travelers is unpredictable, during a period of almost 10 years, there was only one reported death due to disaster in the five countries most frequently visited by US travelers. Further investigation may identify population-, seasonal-, country-, or location-specific risks from which prevention strategies can be developed.

Fatal Primary Capillary Leak Syndrome in a Late Preterm Newborn.

PubMed

Kulihova, Katarina; Prochazkova, Martina; Semberova, Jana; Janota, Jan

2016-10-01

Primary capillary leak syndrome is a rare disease of unknown etiology, characterized by episodes of vascular collapse and plasma extravasation, which may lead to multiple organ failure. Primary capillary leak is extremely rare in children. The authors report a case of a late preterm newborn with fatal capillary leak syndrome of unknown etiology, manifesting as hypotension unresponsive to treatment, extravasation leading to generalised edema, disseminated intravascular coagulation and finally, multiple organ dysfunction syndrome. Aggressive volumotherapy and a combination of inotropes and high doses of terlipressin did not influence systemic vascular collapse and plasma extravasation. The newborn developed multiple organ failure and died on day 27 of life. Investigations performed failed to reveal any specific cause of capillary leak. This is the first report of a fatal primary capillary leak syndrome in a newborn.

Fatal Cerebral Edema, Seizures, and Hyponatremia After Trazodone Overdose.

PubMed

Avila, Jose David

Trazodone is a serotonin antagonist and reuptake inhibitor that is widely used for the treatment of depression and insomnia. Fatal overdose is rare and usually occurs when combined with other drugs or alcohol. Only a few lethal cases of pure trazodone overdose have been reported, all attributed to cardiotoxicity. We reported a 37-year-old woman who presented after ingesting 6.45 g of trazodone in a suicidal attempt. She was hyponatremic because of the syndrome of inappropriate antidiuretic hormone secretion and, shortly after, had a seizure and developed fatal cerebral edema. Others have described seizures and hyponatremia after pure trazodone overdose, but this is the first report of cerebral edema and death from a neurological complication. Careful monitoring and correction of sodium levels may be necessary in these patients.

Adenocarcinoma of the ethmoid following radiotherapy for bilateral retinoblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowe, L.D.; Lane, R.; Snow, J.B. Jr.

1980-01-01

Adenocarcinoma of the ethmoid sinus is rare, representing only 4 to 8% of malignancies of the paranasal sinuses. An extraordinary case of papillary adenocarcinoma of the ethmoid sinus arising 30 years following high-dose radiotherapy for bilateral retinoblastoma is presented. Second fatal mesenchymal and epithelial primaries have been described in 8.5% of patients with bilateral retinoblastomas previously treated with radiotherapy; however, papillary adenocarcinoma arising within the paranasal sinuses has not been reported. Aggressive treatment including partial maxillectomy, radical pansinusectomy, radical neck dissection followed by regional radiotherapy and systemic chemotherapy failed to prevent the development of fatal hepatic metastases. The high incidencemore » of second fatal primary neoplasms in patients with bilateral retinoblastomas receiving radiation suggests an innate susceptibility that may add to the risk of radiotherapy.« less

Opportunities for reduction of fatalities in vehicle-guardrail collisions.

PubMed

Gabler, Hampton C; Gabauer, Douglas J

2007-01-01

In the United States in 2005, there were 1,189 fatal crashes and 35,000 injurious crashes into guardrails. Current efforts to reduce fatalities occurring in guardrail collisions have focused on frontal oblique collisions of cars and light trucks into guardrail. These crashes however represent a diminishing target population for fatality reduction. This paper examines the current opportunities for reducing fatalities in guardrail collisions in the United States. The analysis was based upon crash data from the Fatality Analysis Reporting System (FARS) and the National Automotive Sampling System General Estimates System (GES) for the years 2000-2005. The greatest opportunity for fatality reduction is the protection of motorcyclists, who now account for 32% of guardrail fatalities, and car and light truck occupants in side impact, who now comprise 14% of all guardrail fatalities. Together, protection of motorcycle riders and protection of car and light truck occupants in side impacts account for nearly half of all fatalities (46%) which occur in vehicle-guardrail collisions. Additional targets for fatality reduction include light truck rollover and collisions with guardrail ends.

Prostaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production

NASA Astrophysics Data System (ADS)

Sugita, Kazunari; Ikenouchi-Sugita, Atsuko; Nakayama, Yasuko; Yoshioka, Haruna; Nomura, Takashi; Sakabe, Jun-Ichi; Nakahigashi, Kyoko; Kuroda, Etsushi; Uematsu, Satoshi; Nakamura, Jun; Akira, Shizuo; Nakamura, Motonobu; Narumiya, Shuh; Miyachi, Yoshiki; Tokura, Yoshiki; Kabashima, Kenji

2013-10-01

Pellagra is a photosensitivity syndrome characterized by three ``D's'': diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE2 production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE2 production via induction of ROS formation.

Fatal cervical spine injuries: a Finnish nationwide register-based epidemiologic study on data from 1987 to 2010.

PubMed

Thesleff, Tuomo; Niskakangas, Tero; Luoto, Teemu M; Öhman, Juha; Ronkainen, Antti

2016-08-01

The number of cervical spine injuries (CSIs) is increasing. Cervical spine injuries are associated with high morbidity and mortality. Identifying those who are at risk for CSI-related death can help develop national and international interventions and policies to reduce mortality. This study aimed to determine the trends in the incidence and the characteristics of fatal CSIs in Finland over a 24-year study period from 1987 to 2010. A large nationwide, retrospective, register-based study was carried out. The population-based sample was collected from death certificates issued in Finland between 1987 and 2010. The death certificates were obtained from the official Cause-of-Death Register, coordinated by Statistics Finland, which covers all deaths occurring in Finland. Sociodemographics and injury- and death-related data were used for outcome measures. All death certificates issued in Finland (1987-2010) containing a CSI as the cause of death were carefully reviewed. A total of 2,041 fatal CSIs were identified. These constituted 0.17% of all deaths in Finland within the study period. The average annual incidence of fatal CSIs was 16.5 per million (range: 12.5-21.2). The majority of the victims were male (72.9%) and had concurrent spinal cord injury (83.0%). Traffic accidents (40.1%) and falls (45.0%) were the most common injury mechanisms. Almost one-third (29.8%) of the deaths were alcohol-related. Among the young victims (<60 years) with upper CSI (C0-C2), the majority (91.8%) died within 24 hours post-injury. One-third of elderly victims' (≥60 years) CSI-related deaths occurred after 1 week post-injury and were mostly (74.2%) caused by respiratory and circulatory system diseases. Within the 24-year period, the incidence of fatal CSIs (+2/million), as well as the average age of sustaining a fatal CSI (+13.5 years), increased markedly. Fall-induced accidents among elderly males were the most prominently increasing subpopulation of fatal CSI victims. In recent decades, fatal CSI incidence (death certificate-based) has increased, being 18.6 per million in Finland in 2010. Victims of fatal CSIs tend to be older than in the past, and for a substantial number of males, low-energy falls lead to cervical trauma and death. Copyright © 2015 Elsevier Inc. All rights reserved.

Landslide fatalities in the Western Ghats of Kerala, India

NASA Astrophysics Data System (ADS)

Lukose Kuriakose, Sekhar; Sankar, G.; Muraleedharan, C.

2010-05-01

The Western Ghats of Kerala, India is prone to shallow landslides and consequent debris flows. An earlier study (Kuriakose et al., EG, 2009) has compiled and presented the history and chorology of landslide prone areas of the region. An attempt to collect and compile a reliable fatal landslide inventory of the region resulted in a database of 63 landslides from 1961 to 2009. The data base was compiled from the news paper reports and research reports of the CESS and GSI. Most landslides were visited in and the locations were mapped using a handheld GPS. Date and fatality information was also collected. For twelve of the landslides accurate location information was not available and hence was plotted at the nearest known village centre. Three landslides did not have any location information but was recorded in the district gazetteer and hence included in the data base. A total of 257 valuable lives were lost in landslides. The landslide that caused the highest number of deaths was the Amboori landslide (Thiruvananthapuram) which occurred on 11 September 2001 that caused 39 fatalities. Idukki district experienced the largest number of fatal landslides during this period, 20 events resulting in 67 fatalities. Thiruvananthapuram district experienced the highest average number of fatalities per landslide (47 deaths from 5 events). The district wise statistics from north to south are, Kannur (6 from 5), Kasargodu (24 from 6), Wayanad (36 from 6), Kozhikode (44 from 10), Malappuram (9 from 3), Palakkad (3 from 3), Thrissur (2 from 1), Kottayam (5 from 3), and Pathanamthitta (14 from 3). It was noted that there exists a spatial trend in the occurrence of fatal landslides which follows the general monsoon rainfall trends and the population density. About 55% of the events occurred during the south west monsoon (June to September) season. It was also observed that there exists a strong upward trend in the number of fatal landslides. This upward trend can be directly attributed to the increased migration of people from the plains to the high lands in the mid 1970's and the resultant clearing of natural forests for agriculture and infrastructural development. This upward trend may continue given the population pressure and the expected increase in the frequency of prolonged high intensity rainfall events owing to the effects of climate change on the Indian Monsoon System.

Preliminary analysis of the National Crash Severity Study : factors in fatal accidents

DOT National Transportation Integrated Search

1979-06-01

This study investigates the fatalities on the National Crash Severity Study (NCSS) of towaway, passenger car accidents. The analysis is in three stages. First, NCSS fatalities are compared to the fatally-injured occupants reported on the Fatal Accide...

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS).

PubMed

Dancer, Rachel C A; Parekh, Dhruv; Lax, Sian; D'Souza, Vijay; Zheng, Shengxing; Bassford, Chris R; Park, Daniel; Bartis, D G; Mahida, Rahul; Turner, Alice M; Sapey, Elizabeth; Wei, Wenbin; Naidu, Babu; Stewart, Paul M; Fraser, William D; Christopher, Kenneth B; Cooper, Mark S; Gao, Fang; Sansom, David M; Martineau, Adrian R; Perkins, Gavin D; Thickett, David R

2015-07-01

Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated. To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity. Human, murine and in vitro primary alveolar epithelial cell work were included in this study. Vitamin D deficiency (plasma 25(OH)D levels <50 nmol/L) was ubiquitous in patients with ARDS and present in the vast majority of patients at risk of developing ARDS following oesophagectomy. In a murine model of intratracheal lipopolysaccharide challenge, dietary-induced vitamin D deficiency resulted in exaggerated alveolar inflammation, epithelial damage and hypoxia. In vitro, vitamin D has trophic effects on primary human alveolar epithelial cells affecting >600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients. Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed. UKCRN ID 11994. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

States with low non-fatal injury rates have high fatality rates and vice-versa.

PubMed

Mendeloff, John; Burns, Rachel

2013-05-01

State-level injury rates or fatality rates are sometimes used in studies of the impact of various safety programs or other state policies. How much does the metric used affect the view of relative occupational risks among U.S. states? This paper uses a measure of severe injuries (fatalities) and of less severe injuries (non-fatal injuries with days away from work, restricted work, or job transfer-DART) to examine that issue. We looked at the correlation between the average DART injury rate (from the BLS Survey of Occupational Injuries and Illnesses) and an adjusted average fatality rate (from the BLS Census of Fatal Occupational Injuries) in the construction sector for states for 2003-2005 and for 2006-2008. The RAND Human Subjects Protection Committee determined that this study was exempt from review. The correlations between the fatal and non-fatal injury rates were between -0.30 and -0.70 for all construction and for the subsector of special trade contractors. The negative correlation was much smaller between the rate of fatal falls from heights and the rate of non-fatal falls from heights. Adjusting for differences in the industry composition of the construction sector across states had minor effects on these results. Although some have suggested that fatal and non-fatal injury rates should not necessarily be positively correlated, no one has suggested that the correlation is negative, which is what we find. We know that reported non-fatal rates are influenced by workers' compensation benefits and other factors. Fatality rates appear to be a more valid measure of risk. Efforts to explain the variations that we find should be undertaken. Copyright © 2012 Wiley Periodicals, Inc.

Impact of the effect of economic crisis and the targeted motorcycle safety programme on motorcycle-related accidents, injuries and fatalities in Malaysia.

PubMed

Law, T H; Umar, R S Radin; Zulkaurnain, S; Kulanthayan, S

2005-03-01

In 1997, a Motorcycle Safety Programme (MSP) was introduced to address the motorcycle-related accident problem. The MSP was specifically targeted at motorcyclists. In addition to the MSP, the recent economic recession has significantly contributed to a reduction of traffic-related incidents. This paper examines the effects of the recent economic crisis and the MSP on motorcycle-related accidents, casualties and fatalities in Malaysia. The autocorrelation integrated moving average model with transfer function was used to evaluate the overall effects of the interventions. The variables used in developing the model were gross domestic product and MSPs. The analysis found a 25% reduction in the number of motorcycle-related accidents, a 27% reduction in motorcycle casualties and a 38% reduction in motorcycle fatalities after the implementation of MSP. Findings indicate that the MSP has been one of the effective measures in reducing motorcycle safety problems in Malaysia. Apart from that, the performance of the country's economy was also found to be significant in explaining the number of motorcycle-related accidents, casualties and fatalities in Malaysia.

Mortuary operations following mass fatality natural disasters: a review.

PubMed

Anderson, Madelyn; Leditschke, Jodie; Bassed, Richard; Cordner, Stephen M; Drummer, Olaf H

2017-03-01

This is a critical review to discuss the best practice approaches to mortuary operations in preparation for and the response to natural, mass fatality, disaster events, as identified by a review of published articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) Statement guided the identification of potential articles to use in this critical review. Subsequent searches were also conducted to identify articles relating to heat wave, and flood mortality. All identified peer-reviewed studies published in English which discussed the preparation and response of mortuaries to mass fatality natural disasters occurring in developed countries were included. Using the PRISMA-P method of identifying articles, 18 articles were selected for inclusion in this review. Although there are numerous articles which describe the mortuary response to mass fatality incidents, few articles analyzed the response, or discussed the roles which supported and enabled the organization to undertake the task of identifying disaster victims. It is thus difficult to determine objectively if the actions and activities outlined in the articles represent best-practice.

Estimation of number of fatalities caused by toxic gases due to fire in road tunnels.

PubMed

Qu, Xiaobo; Meng, Qiang; Liu, Zhiyuan

2013-01-01

The quantitative risk assessment (QRA) is one of the explicit requirements under the European Union (EU) Directive (2004/54/EC). As part of this, it is essential to be able to estimate the number of fatalities in different accident scenarios. In this paper, a tangible methodology is developed to estimate the number of fatalities caused by toxic gases due to fire in road tunnels by incorporating traffic flow and the spread of fire in tunnels. First, a deterministic queuing model is proposed to calculate the number of people at risk, by taking into account tunnel geometry, traffic flow patterns, and incident response plans for road tunnels. Second, the Fire Dynamics Simulator (FDS) is used to obtain the temperature and concentrations of CO, CO(2), and O(2). By taking advantage of the additivity of the fractional effective dose (FED) method, fatality rates for different locations in given time periods can be estimated. An illustrative case study is carried out to demonstrate the applicability of the proposed methodology. Copyright © 2012 Elsevier Ltd. All rights reserved.

MITOCHONDRIAL DNA DEPLETION SYNDROME DUE TO MUTATIONS IN THE RRM2B GENE

PubMed Central

Bornstein, Belén; Area, Estela; Flanigan, Kevin M.; Ganesh, Jaya; Jayakar, Parul; Swoboda, Kathryn J.; Coku, Jorida; Naini, Ali; Shanske, Sara; Tanji, Kurenai; Hirano, Michio; DiMauro, Salvatore

2014-01-01

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in The RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in 7 infants from 4 families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at three months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exon 6, 8 and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy. PMID:18504129

Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene.

PubMed

Bornstein, Belén; Area, Estela; Flanigan, Kevin M; Ganesh, Jaya; Jayakar, Parul; Swoboda, Kathryn J; Coku, Jorida; Naini, Ali; Shanske, Sara; Tanji, Kurenai; Hirano, Michio; DiMauro, Salvatore

2008-06-01

Mitochondrial DNA depletion syndrome (MDS) is characterized by a reduction in mtDNA copy number and has been associated with mutations in eight nuclear genes, including enzymes involved in mitochondrial nucleotide metabolism (POLG, TK2, DGUOK, SUCLA2, SUCLG1, PEO1) and MPV17. Recently, mutations in the RRM2B gene, encoding the p53-controlled ribonucleotide reductase subunit, have been described in seven infants from four families, who presented with various combinations of hypotonia, tubulopathy, seizures, respiratory distress, diarrhea, and lactic acidosis. All children died before 4 months of age. We sequenced the RRM2B gene in three unrelated cases with unexplained severe mtDNA depletion. The first patient developed intractable diarrhea, profound weakness, respiratory distress, and died at 3 months. The other two unrelated patients had a much milder phenotype and are still alive at ages 27 and 36 months. All three patients had lactic acidosis and severe depletion of mtDNA in muscle. Muscle histochemistry showed RRF and COX deficiency. Sequencing the RRM2B gene revealed three missense mutations and two single nucleotide deletions in exons 6, 8, and 9, confirming that RRM2B mutations are important causes of MDS and that the clinical phenotype is heterogeneous and not invariably fatal in infancy.

Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy

PubMed Central

Tisdale, Sarah

2015-01-01

Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease. PMID:26063904

Genetic partitioning of interleukin-6 signalling in mice dissociates Stat3 from Smad3-mediated lung fibrosis

PubMed Central

O'Donoghue, Robert J J; Knight, Darryl A; Richards, Carl D; Prêle, Cecilia M; Lau, Hui Ling; Jarnicki, Andrew G; Jones, Jessica; Bozinovski, Steven; Vlahos, Ross; Thiem, Stefan; McKenzie, Brent S; Wang, Bo; Stumbles, Philip; Laurent, Geoffrey J; McAnulty, Robin J; Rose-John, Stefan; Zhu, Hong Jian; Anderson, Gary P; Ernst, Matthias R; Mutsaers, Steven E

2012-01-01

Idiopathic pulmonary fibrosis (IPF) is a fatal disease that is unresponsive to current therapies and characterized by excessive collagen deposition and subsequent fibrosis. While inflammatory cytokines, including interleukin (IL)-6, are elevated in IPF, the molecular mechanisms that underlie this disease are incompletely understood, although the development of fibrosis is believed to depend on canonical transforming growth factor (TGF)-β signalling. We examined bleomycin-induced inflammation and fibrosis in mice carrying a mutation in the shared IL-6 family receptor gp130. Using genetic complementation, we directly correlate the extent of IL-6-mediated, excessive Stat3 activity with inflammatory infiltrates in the lung and the severity of fibrosis in corresponding gp130757F mice. The extent of fibrosis was attenuated in B lymphocyte-deficient gp130757F;µMT−/− compound mutant mice, but fibrosis still occurred in their Smad3−/− counterparts consistent with the capacity of excessive Stat3 activity to induce collagen 1α1 gene transcription independently of canonical TGF-β/Smad3 signalling. These findings are of therapeutic relevance, since we confirmed abundant STAT3 activation in fibrotic lungs from IPF patients and showed that genetic reduction of Stat3 protected mice from bleomycin-induced lung fibrosis. PMID:22684844

Autophagy and Mis-targeting of Therapeutic Enzyme in Skeletal Muscle in Pompe Disease

PubMed Central

Fukuda, Tokiko; Ahearn, Meghan; Roberts, Ashley; Mattaliano, Robert J.; Zaal, Kristien; Ralston, Evelyn; Plotz, Paul H.; Raben, Nina

2009-01-01

Enzyme replacement therapy (ERT) became a reality for patients with Pompe disease, a fatal cardiomyopathy and skeletal muscle myopathy caused by a deficiency of glycogen-degrading lysosomal enzyme acid alpha-glucosidase (GAA). The therapy, which relies on receptor-mediated endocytosis of recombinant human GAA (rhGAA), appears to be effective in cardiac muscle, but less so in skeletal muscle. We have previously shown a profound disturbance of the lysosomal degradative pathway (autophagy) in therapy-resistant muscle of GAA knockout mice (KO). Our findings here demonstrate a progressive age-dependent autophagic build-up in addition to enlargement of glycogen-filled lysosomes in multiple muscle groups in the KO. Trafficking and processing of the therapeutic enzyme along the endocytic pathway appear to be affected by the autophagy. Confocal microscopy of live single muscle fibers exposed to fluorescently labeled rhGAA indicates that a significant portion of the endocytosed enzyme in the KO was trapped as a partially processed form in the autophagic areas instead of reaching its target – the lysosomes. A fluid-phase endocytic marker was similarly mis-targeted and accumulated in vesicular structures within the autophagic areas. These findings may explain why ERT often falls short of reversing the disease process, and point to new avenues for the development of pharmacological intervention. PMID:17008131

Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis

PubMed Central

Woehrl, Bianca; Brouwer, Matthijs C.; Murr, Carmen; Heckenberg, Sebastiaan G.B.; Baas, Frank; Pfister, Hans W.; Zwinderman, Aeilko H.; Morgan, B. Paul; Barnum, Scott R.; van der Ende, Arie; Koedel, Uwe; van de Beek, Diederik

2011-01-01

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor–deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis. PMID:21926466

Occupational Carbon Monoxide Fatalities in the US From Unintentional Non-Fire Related Exposures, 1992–2008

PubMed Central

Henn, Scott A.; Bell, Jennifer L.; Sussell, Aaron L.; Konda, Srinivas

2015-01-01

Objective To analyze characteristics of, and trends in, work-related carbon monoxide (CO) fatalities in the US. Methods Records of unintentional, non-fire related fatalities from CO exposure were extracted from the Bureau of Labor Statistics’ Census of Fatal Occupational Injuries and the Occupational Safety and Health Administration’s Integrated Management Information System for years 1992–2008 and analyzed separately. Results The average number of annual CO fatalities was 22 (standard deviation = 8). Fatality rates were highest among workers aged ≥65, males, Hispanics, winter months, the Midwest, and the Fishing, Hunting, and Trapping industry subsector. Self-employed workers accounted for 28% of all fatalities. Motor vehicles were the most frequent source of fatal CO exposure, followed by heating systems and generators. Conclusions CO has been the most frequent cause of occupational fatality due to acute inhalation, and has shown no significant decreasing trend since 1992. The high number of fatalities from motor vehicles warrants further investigation. PMID:23868822

Pedestrian and bicyclist fatalities in large truck crashes, 2013 : [analysis brief].

DOT National Transportation Integrated Search

2015-11-01

From 2006 to 2013, pedestrian fatalities as a : percentage of total fatalities in all motor vehicle : crashes rose from 11.2 percent to 14.5 percent, and : bicyclist fatalities as a percentage of total fatalities : rose from 1.8 percent to 2.3 percen...

G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

PubMed

Dombrowski, Jamille G; Souza, Rodrigo M; Curry, Jonathan; Hinton, Laura; Silva, Natercia R M; Grignard, Lynn; Gonçalves, Ligia A; Gomes, Ana Rita; Epiphanio, Sabrina; Drakeley, Chris; Huggett, Jim; Clark, Taane G; Campino, Susana; Marinho, Claudio R F

2017-06-15

Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. Five-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay. Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. The data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.

An insight into the maritime accident characteristics in Bangladesh

NASA Astrophysics Data System (ADS)

Uddin, Md. Imran; Awal, Zobair Ibn

2017-12-01

The inland waterway plays a very important role in the transportation system of Bangladesh. But, due to severe deficiencies of the safety practices, a lot of accidentll take place almost every year in the inland waterways that cause considerable loss of human lives and assets. The inland waterway accidentll in Bangladasb during 2005 to 2015 were analysed statistically in the present study. It has been found that the leading mode of accidents is collision among vessels and fatal injury comprises considerably a higher proportion of total casnalties. The study also revealed that cargo vessels and passenger vessels encounter more accidents in comparison to other types of vessels. It was also observed that during fair weather and good visibility condition significant proportion of accidents have taken place. Based on this study several recommendstions bsve been put forward for improving ssfety in the inlsnd waterways ofBanglsdesh.

The refeeding syndrome. Importance of phosphorus.

PubMed

Araujo Castro, Marta; Vázquez Martínez, Clotilde

2018-06-22

Refeeding syndrome (RS) is a complex disease that occurs when nutritional support is initiated after a period of starvation. The hallmark feature is the hypophosphataemia, however other biochemical abnormalities like hypokalaemia, hypomagnesaemia, thiamine deficiency and disorder of sodium and fluid balance are common. The incidence of RS is unknown as no universally accepted definition exists, but it is frequently underdiagnosed. RS is a potentially fatal, but preventable, disorder. The identification of patients at risk is crucial to improve their management. If RS is diagnosed, there is one guideline (NICE 2006) in place to help its treatment (but it is based on low quality of evidence). The aims of this review are: highlight the importance of this problem in malnourished patients, discuss the pathophysiology and clinical characteristics, with a final series of recommendations to reduce the risk of the syndrome and facilitate the treatment. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice.

PubMed

Petkau, Terri L; Zhu, Shanshan; Lu, Ge; Fernando, Sarah; Cynader, Max; Leavitt, Blair R

2013-11-01

Loss-of-function mutations in the progranulin (GRN) gene are a common cause of autosomal dominant frontotemporal lobar degeneration, a fatal and progressive neurodegenerative disorder common in people less than 65 years of age. In the brain, progranulin is expressed in multiple regions at varying levels, and has been hypothesized to play a neuroprotective or neurotrophic role. Four neurotoxic agents were injected in vivo into constitutive progranulin knockout (Grn(-/-)) mice and their wild-type (Grn(+/+)) counterparts to assess neuronal sensitivity to toxic stress. Administration of 3-nitropropionic acid, quinolinic acid, kainic acid, and pilocarpine induced robust and measurable neuronal cell death in affected brain regions, but no differential cell death was observed between Grn(+/+) and Grn(-/-) mice. Thus, constitutive progranulin knockout mice do not have increased sensitivity to neuronal cell death induced by the acute chemical models of neuronal injury used in this study. Copyright © 2013. Published by Elsevier Inc.

Incidences and variations of hospital acquired venous thromboembolism in Australian hospitals: a population-based study.

PubMed

Assareh, Hassan; Chen, Jack; Ou, Lixin; Hillman, Ken; Flabouris, Arthas

2016-09-22

Data on hospital-acquired venous thromboembolism (HA-VTE) incidence, case fatality rate and variation amongst patient groups and health providers is lacking. We aim to explore HA-VTE incidences, associated mortality, trends and variations across all acute hospitals in New South Wales (NSW)-Australia. A population-based study using all admitted patients (aged 18-90 with a length of stay of at least two days and not transferred to another acute care facility) in 104 NSW acute public and private hospitals during 2002-2009. Poisson mixed models were used to derive adjusted rate ratios (IRR) in presence of patient and hospital characteristics. Amongst, 3,331,677 patients, the incidence of HA-VTE was 11.45 per 1000 patients and one in ten who developed HA-VTE died in hospital. HA-VTE incidence, initially rose, but subsequently declined, whereas case fatality rate consistently declined by 22 % over the study period. Surgical patients were 128 % (IRR = 2.28, 95 % CI: 2.19-2.38) more likely to develop HA-VTE, but had similar case fatality rates compared to medical patients. Private hospitals, in comparison to public hospitals had a higher incidence of HA-VTE (IRR = 1.76; 95 % CI: 1.42-2.18) for medical patients. However, they had a similar incidence (IRR = 0.91; 95 % CI: 0.75-1.11), but a lower mortality (IRR = 0.59; 95 % CI: 0.47-0.75) amongst surgical patients. Smaller public hospitals had a lower HA-VTE incidence rate compared to larger hospitals (IRR < 0.68) but a higher case fatality rate (IRR > 1.71). Hospitals with a lower reported HA-VTE incidence tended to have a higher HA-VTE case fatality rate. Despite the decline in HA-VTE incidence and case fatality, there were large variations in incidents between medical and surgical patients, public and private hospitals, and different hospital groups. The causes of such differences warrant further investigation and may provide potential for targeted interventions and quality improvement initiatives.

Machinery-related occupational fatalities in the United States, 1980 to 1989.

PubMed

Pratt, S G; Kisner, S M; Helmkamp, J C

1996-01-01

The National Traumatic Occupational Fatalities surveillance system identified machinery-related incidents as the second leading cause of traumatic occupational fatalities in the United States between 1980 and 1989. These incidents resulted in 8,505 civilian worker deaths and an average annual fatality rate of .80 per 100,000 workers. Workers aged 65 years and older had 5.8 times the fatality rate of workers aged 16 to 64 years (4.06 vs. 70). The highest industry-specific rate was noted in agriculture, forestry, and fishing (7.47). Tractors and other agricultural machinery were associated with nearly 9 of every 10 fatal machinery-related incidents involving workers aged 65 or older. Although numerous studies of agricultural machinery-related fatalities are found in the literature, detailed analyses of machinery-related fatalities in the construction industry as well as analyses of work situations and risk factors associated with fatal injuries are needed.

New evidence concerning fatal crashes of passenger vehicles before and after adding antilock braking systems.

PubMed

Farmer, C M

2001-05-01

Fatal crash rates for passenger cars and vans were compared for the last model year before four-wheel antilock brakes were introduced and the first model year for which antilock brakes were standard equipment. A prior study, based on fatal crash experience through 1995, reported that vehicle models with antilock brakes were more likely than identical but 1-year-earlier models to be involved in crashes fatal to their own occupants, but were less likely to be involved in crashes fatal to occupants of other vehicles. Overall, there was no significant effect of antilocks on the likelihood of fatal crashes. Similar analyses, based on fatal crash experience during 1996-98, yielded very different results. During 1996-98, vehicles with antilock brakes were again less likely than earlier models to be involved in crashes fatal to occupants of other vehicles, but they were no longer overinvolved in crashes fatal to their own occupants.

Construction fatality due to electrical contact in Ontario, Canada, 1997-2007.

PubMed

Kim, Hwan; Lewko, John; Garritano, Enzo; Sharma, Bhanu; Moody, Joel; Colantonio, Angela

2016-06-27

Electrical contact is a leading cause of occupational fatality in the construction industry. However, research on the factors that contribute to electricity-related fatality in construction is limited. To characterize, using an adapted Haddon's Matrix, the factors that contribute to electricity-related occupational fatalities in the construction industry in Ontario, Canada. Coroner's data on occupational electricity-related fatalities between 1997-2007 in the construction industry were acquired from the Ontario Ministry of Labour. Using an adapted Haddon's Matrix, we characterized worker, agent, and environmental characteristics of electricity-related occupational fatalities in the province through a narrative text analysis. Electrical contact was responsible for 15% of all occupational fatalities among construction workers in Ontario. Factors associated with said occupational fatalities included direct contact with electrical sources, lower voltage sources, and working outdoors. This study provides a profile of electricity-related occupational fatalities among construction workers in Ontario, and can be used to inform safety regulations.

Fatal accidents at railway level crossings in Great Britain 1946-2009.

PubMed

Evans, Andrew W

2011-09-01

This paper investigates fatal accidents and fatalities at level crossings in Great Britain over the 64-year period 1946-2009. The numbers of fatal accidents and fatalities per year fell by about 65% in the first half of that period, but since then have remained more or less constant at about 11 fatal accidents and 12 fatalities per year. At the same time other types of railway fatalities have fallen, so level crossings represent a growing proportion of the total. Nevertheless, Britain's level crossing safety performance remains good by international standards. The paper classifies level crossings into three types: railway-controlled, automatic, and passive. The safety performance of the three types of crossings has been very different. Railway-controlled crossings are the best-performing crossing type, with falling fatal accident rates. Automatic crossings have higher accident rates per crossing than railway controlled or passive crossings, and the accident rates have not decreased. Passive crossings are by far the most numerous, but many have low usage by road users. Their fatal accident rate has remained remarkably constant over the whole period at about 0.9 fatal accidents per 1000 crossings per year. A principal reason why fatal accidents and fatalities have not fallen in the second half of the period as they did in the first half is the increase in the number of automatic crossings, replacing the safer railway controlled crossings on some public roads. However, it does not follow that this replacement was a mistake, because automatic crossings have advantages over controlled crossings in reducing delays to road users and in not needing staff. Based on the trends for each type of crossing and for pedestrian and non-pedestrian accidents separately, in 2009 a mean of about 5% of fatal accidents were at railway controlled crossings, 52% were at automatic crossings, and 43% were at passive crossings. Fatalities had similar proportions. About 60% of fatalities were to pedestrians. A simple comparison of automatic railway level crossings and signalised road intersections found that in 2005 the numbers of fatalities per 1000 crossings or intersections were similar. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluating the Effectiveness of an Ultrasonic Acoustic Deterrent for Reducing Bat Fatalities at Wind Turbines.

PubMed

Arnett, Edward B; Hein, Cris D; Schirmacher, Michael R; Huso, Manuela M P; Szewczak, Joseph M

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21-51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities.

Evaluating the Effectiveness of an Ultrasonic Acoustic Deterrent for Reducing Bat Fatalities at Wind Turbines

PubMed Central

Arnett, Edward B.; Hein, Cris D.; Schirmacher, Michael R.; Huso, Manuela M. P.; Szewczak, Joseph M.

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21–51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities. PMID:23840369

Evaluating the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at wind turbines

USGS Publications Warehouse

Arnett, Edward B.; Hein, Cris D.; Schirmacher, Michael R.; Huso, Manuela M.P.; Szewczak, Joseph M.

2013-01-01

Large numbers of bats are killed by wind turbines worldwide and minimizing fatalities is critically important to bat conservation and acceptance of wind energy development. We implemented a 2-year study testing the effectiveness of an ultrasonic acoustic deterrent for reducing bat fatalities at a wind energy facility in Pennsylvania. We randomly selected control and treatment turbines that were searched daily in summer and fall 2009 and 2010. Estimates of fatality, corrected for field biases, were compared between treatment and control turbines. In 2009, we estimated 21–51% fewer bats were killed per treatment turbine than per control turbine. In 2010, we determined an approximate 9% inherent difference between treatment and control turbines and when factored into our analysis, variation increased and between 2% more and 64% fewer bats were killed per treatment turbine relative to control turbines. We estimated twice as many hoary bats were killed per control turbine than treatment turbine, and nearly twice as many silver-haired bats in 2009. In 2010, although we estimated nearly twice as many hoary bats and nearly 4 times as many silver-haired bats killed per control turbine than at treatment turbines during the treatment period, these only represented an approximate 20% increase in fatality relative to the pre-treatment period for these species when accounting for inherent differences between turbine sets. Our findings suggest broadband ultrasound broadcasts may reduce bat fatalities by discouraging bats from approaching sound sources. However, effectiveness of ultrasonic deterrents is limited by distance and area ultrasound can be broadcast, in part due to rapid attenuation in humid conditions. We caution that an operational deterrent device is not yet available and further modifications and experimentation are needed. Future efforts must also evaluate cost-effectiveness of deterrents in relation to curtailment strategies to allow a cost-benefit analysis for mitigating bat fatalities.

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed

Stout, N; Bell, C

1991-06-01

The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems.

Effectiveness of source documents for identifying fatal occupational injuries: a synthesis of studies.

PubMed Central

Stout, N; Bell, C

1991-01-01

BACKGROUND: The complete and accurate identification of fatal occupational injuries among the US work force is an important first step in developing work injury prevention efforts. Numerous sources of information, such as death certificates, Workers' Compensation files, Occupational Safety and Health Administration (OSHA) files, medical examiner records, state health and labor department reports, and various combinations of these, have been used to identify cases of work-related fatal injuries. Recent studies have questioned the effectiveness of these sources for identifying such cases. METHODS: At least 10 studies have used multiple sources to define the universe of fatal work injuries within a state and to determine the capture rates, or proportion of the universe identified, by each source. Results of these studies, which are not all available in published literature, are summarized here in a format that allows researchers to readily compare the ascertainment capabilities of the sources. RESULTS: The overall average capture rates of sources were as follows: death certificates, 81%; medical examiner records, 61%; Workers' Compensation reports, 57%; and OSHA reports 32%. Variations by state and value added through the use of multiple sources are presented and discussed. CONCLUSIONS: This meta-analysis of 10 state-based studies summarizes the effectiveness of various source documents for capturing cases of fatal occupational injuries to help researchers make informed decisions when designing occupational injury surveillance systems. PMID:1827569

Fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery for a pituitary tumor: A case report.

PubMed

Li, Chiao-Zhu; Li, Chiao-Ching; Hsieh, Chih-Chuan; Lin, Meng-Chi; Hueng, Dueng-Yuan; Liu, Feng-Chen; Chen, Yuan-Hao

2017-01-01

The fatal type of antiphospholipid syndrome is a rare but life-threating condition. It may be triggered by surgery or infection. Endoscopic transnasal-transsphenoidal surgery is a common procedure for pituitary tumor. We report a catastrophic case of a young woman died of fatal antiphospholipid syndrome following endoscopic transnasal-transsphenoidal surgery. A 31-year-old woman of a history of stroke received endoscopic transnasal-transsphenoidal surgery for a pituitary tumor. The whole procedure was smooth. However, the patient suffered from acute delirium on postoperative day 4. Then, her consciousness became comatose state rapidly with dilatation of pupils. Urgent magnetic resonance imaging of brain demonstrated multiple acute lacunar infarcts. The positive antiphosphoipid antibody and severe thrombocytopenia were also noted. Fatal antiphospholipid syndrome was diagnosed. Plasma exchange, corticosteroids, anticoagulant agent were prescribed. The hemodynamic condition was gradually stable. However, the consciousness was still in deep coma. The patient died of organ donation 2 months later. If patients have a history of cerebral stroke in their early life, such as a young stroke, the APS and higher risk of developing fatal APS after major surgery should be considered. The optimal management of APS remains controversial. The best treatment strategies are only early diagnosis and aggressive therapies combing of anticoagulant, corticosteroid, and plasma exchange. The intravenous immunoglobulin is prescribed for patients with refractory APS.

Identifying high-risk small business industries for occupational safety and health interventions.

PubMed

Okun, A; Lentz, T J; Schulte, P; Stayner, L

2001-03-01

Approximately one-third (32%) of U.S. workers are employed in small business industries (those with 80% of workers in establishments with fewer than 100 employees), and approximately 53 million persons in private industry work in small business establishments. This study was performed to identify small business industries at high risk for occupational injuries, illnesses, and fatalities. Small business industries were identified from among all three- and four-digit Standard Industrial Classification (SIC) codes and ranked using Bureau of Labor Statistics (BLS) data by rates and numbers of occupational injuries, illnesses, and fatalities. Both incidence rates and number of injury, illness, and fatality cases were evaluated. The 253 small business industries identified accounted for 1,568 work-related fatalities (34% of all private industry). Transportation incidents and violent acts were the leading causes of these fatalities. Detailed injury and illness data were available for 105 small business industries, that accounted for 1,476,400 work-related injuries, and 55,850 occupational illnesses. Many of the small business industries had morbidity and mortality rates exceeding the average rates for all private industry. The highest risk small business industries, based on a combined morbidity and mortality index, included logging, cut stone and stone products, truck terminals, and roofing, siding, and sheet metal work. Identification of high-risk small business industries indicates priorities for those interested in developing targeted prevention programs.

Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.

PubMed

Quarello, Paola; Tandoi, Francesco; Carraro, Francesca; Vassallo, Elena; Pinon, Michele; Romagnoli, Renato; David, Ezio; Dell Olio, Dominic; Salizzoni, Mauro; Fagioli, Franca; Calvo, Pier Luigi

2018-05-01

Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiencies. However, pre-HSCT conditioning entails unacceptably high risks if the liver is compromised. The presence of a recurrent opportunistic infection affecting the biliary tree and determining liver cirrhosis with portal hypertension posed particular decisional difficulties in a 7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the scanty experience available on such rare cases, as successful management with sequential liver transplantation (LT) and HSCT has been reported in detail only in 1 young adult to date. A closely sequential strategy, with a surgical complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to be performed only one month after LT, preventing Cryptosporidium parvum recolonization of the liver graft. Combined sequential LT and HSCT resolved the cirrhotic evolution and corrected the immunodeficiency so that the infection responsible for the progressive sclerosing cholangitis did not recur. Hopefully, this report of the successful resolution of a potentially fatal combination of immunodeficiency and chronic opportunistic infection with end-stage organ damage in a child will encourage others to adapt a sequential transplant approach to this highly complex pathology. However, caution is to be exercised to carefully balance the risks intrinsic to transplant surgery and immunosuppression in primary immunodeficiencies.

Failed CTL/NK cell killing and cytokine hypersecretion are directly linked through prolonged synapse time

PubMed Central

Rudd-Schmidt, Jesse A.; Lopez, Jamie A.; Ramsbottom, Kelly M.; Mannering, Stuart I.; Andrews, Daniel M.; Voskoboinik, Ilia

2015-01-01

Failure of cytotoxic T lymphocytes (CTLs) or natural killer (NK) cells to kill target cells by perforin (Prf)/granzyme (Gzm)-induced apoptosis causes severe immune dysregulation. In familial hemophagocytic lymphohistiocytosis, Prf-deficient infants suffer a fatal “cytokine storm” resulting from macrophage overactivation, but the link to failed target cell death is not understood. We show that prolonged target cell survival greatly amplifies the quanta of inflammatory cytokines secreted by CTLs/NK cells and that interferon-γ (IFN-γ) directly invokes the activation and secondary overproduction of proinflammatory IL-6 from naive macrophages. Furthermore, using live cell microscopy to visualize hundreds of synapses formed between wild-type, Prf-null, or GzmA/B-null CTLs/NK cells and their targets in real time, we show that hypersecretion of IL-2, TNF, IFN-γ, and various chemokines is linked to failed disengagement of Prf- or Gzm-deficient lymphocytes from their targets, with mean synapse time increased fivefold, from ∼8 to >40 min. Surprisingly, the signal for detachment arose from the dying target cell and was caspase dependent, as delaying target cell death with various forms of caspase blockade also prevented their disengagement from fully competent CTLs/NK cells and caused cytokine hypersecretion. Our findings provide the cellular mechanism through which failed killing by lymphocytes causes systemic inflammation involving recruitment and activation of myeloid cells. PMID:25732304

Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency.

PubMed

Pliss, Lioudmila; Jatania, Urvi; Patel, Mulchand S

2016-06-01

Pyruvate dehydrogenase complex (PDC) deficiency is a major inborn error of oxidative metabolism of pyruvate in the mitochondria causing congenital lactic acidosis and primarily structural and functional abnormalities of the central nervous system. To provide an alternate source of acetyl-CoA derived from ketone bodies to the developing brain, a formula high in fat content is widely employed as a treatment. In the present study we investigated efficacy of a high-fat diet given to mothers during pregnancy and lactation on lessening of the impact of PDC deficiency on brain development in PDC-deficient female progeny. A murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene was employed in this study. Maternal consumption of a high-fat diet during pregnancy and lactation had no effect on number of live-birth, body growth, tissue PDC activity levels, as well as the in vitro rates of glucose oxidation and fatty acid biosynthesis by the developing brain of PDC-deficient female offspring during the postnatal age 35 days, as compared to the PDC-deficient progeny born to dams on a chow diet. Interestingly, brain weight was normalized in PDC-deficient progeny of high fat-fed mothers with improvement in impairment in brain structure deficit whereas brain weight was significantly decreased and was associated with greater cerebral structural defects in progeny of chow-fed mothers as compared to control progeny of mothers fed either a chow or high fat diet. The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

Health services in Indonesia.

PubMed

Kosen, S; Gunawan, S

In Indonesia, rapid economic development has led to a reduction in poverty among the 195 million inhabitants. While population increased more than 50% from 1971 to 1990, the annual growth rate, crude birth rate, and total fertility rates have declined rapidly. Life expectancy has increased from 45.7 years in 1971 to 62.7 in 1994 as crude death rates and infant and child mortality rates have declined. Causes of death have shifted from infectious to chronic diseases, but in 1992 major causes of death in children under 5 years old were preventable, and the maternal mortality rate was 425/100,000. Policies which guide the development of health care call for improvements in quality of life, adherence to humanitarian principles, use of scientifically approved traditional medicine, and provision of public health through a three-tiered system. Health care is financed by the government and the community, and managed care has been encouraged. Foreign aid has bolstered development in the health sector. Adequate sanitation has been achieved for 35% of the population, and 65% of urban and 35% of rural residents have reasonable access to clean water. Improvements in health indicators include 55% contraceptive prevalence, reduction in prevalence of anemia during pregnancy, 55.8% of pregnant women receiving prenatal care, a decrease in protein-energy malnutrition among children under five, and high vaccination coverage. Remaining public health problems include malaria, tuberculosis, dengue hemorrhagic fever, an increase in HIV/AIDS, iodine-deficiency, an increasing number of traffic fatalities, and an increasing number of smokers. New health policies have been instituted to meet these challenges as Indonesia's need for a productive and competitive labor force increases.

A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

PubMed

Milligan, Gregg N; Sarathy, Vanessa V; White, Mellodee M; Greenberg, M Banks; Campbell, Gerald A; Pyles, Richard B; Barrett, Alan D T; Bourne, Nigel

2017-10-01

The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

State Traffic Data: Traffic Safety Facts, 2001.

ERIC Educational Resources Information Center

National Center for Statistics and Analysis (NHTSA), Washington, DC.

This brief provides statistical information on U.S. traffic accidents delineated by state. A map details the 2001 traffic fatalities by state and the percent change from 2000. Data tables include: (1) traffic fatalities and fatality rates, 2001; (2) traffic fatalities and percent change, 1975-2001; (3) alcohol involvement in fatal traffic crashes,…

Highway Safety: Trends in Highway Fatalities 1975-1987

DTIC Science & Technology

1990-03-01

pattern of fatalities as the overall trend. This pattern applies to many of the general fatality statis- tics we present, and, in all cases, it serves as a...Fatalities 1975-87 Appemfx IV Vehicle-Related Statistics Figure IV.17: Vehicle Fatalities by Direction of Principal Impacto NNNumber of PddUlsils lwam 0 1975

Fatalism and HIV/AIDS beliefs in rural Mali, West Africa.

PubMed

Hess, Rosanna F; McKinney, Dawn

2007-01-01

To examine beliefs about HIV/AIDS of rural Malians and to measure their level of fatalism in context of HIV/AIDS and prevention behaviors. Descriptive, correlational. An AIDS Knowledge and Beliefs survey and the Powe Fatalism Inventory (PFI)-HIV/AIDS version were administered to a convenience sample of 84 people at three health center maternity clinics in southeastern Mali, West Africa. The sample's HIV/AIDS fatalism mean was 9.2 on a 15-point scale, with an internal consistency of .89. Health workers and more educated participants had significantly lower fatalism scores. Fatalism also varied by the combination of gender and ethnicity. People who believed that AIDS was not real, was a punishment from God, was fabricated by the West, was a curse, and that it was taboo to talk about AIDS had higher fatalism means. None of the prevention indicators were significantly related to fatalism scores. These rural Malians had a high overall fatalism mean and their beliefs about AIDS based on traditional culture may affect prevention behaviors. More research is needed to understand the influence of fatalism on prevention behaviors.

A new method for the production of social fragility functions and the result of its use in worldwide fatality loss estimation for earthquakes

NASA Astrophysics Data System (ADS)

Daniell, James; Wenzel, Friedemann

2014-05-01

A review of over 200 fatality models over the past 50 years for earthquake loss estimation from various authors has identified key parameters that influence fatality estimation in each of these models. These are often very specific and cannot be readily adapted globally. In the doctoral dissertation of the author, a new method is used for regression of fatalities to intensity using loss functions based not only on fatalities, but also using population models and other socioeconomic parameters created through time for every country worldwide for the period 1900-2013. A calibration of functions was undertaken from 1900-2008, and each individual quake analysed from 2009-2013 in real-time, in conjunction with www.earthquake-report.com. Using the CATDAT Damaging Earthquakes Database containing socioeconomic loss information for 7208 damaging earthquake events from 1900-2013 including disaggregation of secondary effects, fatality estimates for over 2035 events have been re-examined from 1900-2013. In addition, 99 of these events have detailed data for the individual cities and towns or have been reconstructed to create a death rate as a percentage of population. Many historical isoseismal maps and macroseismic intensity datapoint surveys collected globally, have been digitised and modelled covering around 1353 of these 2035 fatal events, to include an estimate of population, occupancy and socioeconomic climate at the time of the event at each intensity bracket. In addition, 1651 events without fatalities but causing damage have also been examined in this way. The production of socioeconomic and engineering indices such as HDI and building vulnerability has been undertaken on a country-level and state/province-level leading to a dataset allowing regressions not only using a static view of risk, but also allowing for the change in the socioeconomic climate between the earthquake events to be undertaken. This means that a year 1920 event in a country, will not simply be regressed against a year 2000 event, but normalised. A global human development index (HDI) (life expectancy, education and income) was developed and collected for the first time from 1900-2013 globally on a country and province level allowing for a very useful parameter in the regression. In addition, the occupancy rate from the time of day that the event occurred, as well as population density and individual earthquake attributes like the existence of a foreshock were also examined for the 3004 events in the regression analysis. Where an event has not occurred in a country previously, a regionalisation strategy based on building typologies, seismic code index, building practice, climate, earthquake history and socioeconomic climate is proposed. The result is a set of "social fragility functions" calculating fatalities for use in any country worldwide using the parameters of macroseismic intensity, population, HDI, time of day and occupancy, that provide a robust accurate method, which has not only been calibrated to country level data but to town and city data through time. The estimates will continue to be used in conjunction with Earthquake Report, a non-profit worldwide earthquake reporting website and has shown very promising results from 2010-2013 for rapid estimates of fatalities globally.

Urban sprawl as a risk factor in motor vehicle occupant and pedestrian fatalities.

PubMed

Ewing, Reid; Schieber, Richard A; Zegeer, Charles V

2003-09-01

We sought to determine the association between urban sprawl and traffic fatalities. We created a sprawl index by applying principal components analysis to data for 448 US counties in the largest 101 metropolitan areas. Regression analysis was used to determine associations between the index and traffic fatalities. For every 1% increase in the index (i.e., more compact, less sprawl), all-mode traffic fatality rates fell by 1.49% (P <.001) and pedestrian fatality rates fell by 1.47% to 3.56%, after adjustment for pedestrian exposure (P <.001). Urban sprawl was directly related to traffic fatalities and pedestrian fatalities. Subsequent studies should investigate relationships at a finer geographic scale and should strive to improve on the measure of exposure used to adjust pedestrian fatality rates.

Road traffic fatalities in selected governorates of Iraq from 2010 to 2013: prospective surveillance.

PubMed

Leidman, Eva; Maliniak, Maret; Sultan, Abdul-Salam Saleh; Hassan, Ahmed; Hussain, Syed Jaffar; Bilukha, Oleg O

2016-01-01

The insurgency tactics that characterize modern warfare, such as suicide car bombs and roadside bombs, have the potential to significantly impact road traffic injuries in conflict affected-countries. As road traffic incidents are one of the top ten causes of death in Iraq, changes in incidence have important implications for the health system. We aimed to describe patterns of road traffic fatalities for all demographic groups and types of road users in Iraq during a period characterized by a resurgence in insurgency activity. Iraqi Ministry of Health routine prospective injury surveillance collects information on all fatal injuries in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. From all injury fatalities documented at the coroner office, we analyzed only those attributed to road traffic that occurred between 1 January 2010 and 31 December 2013. Coroners ascertain information from physical examinations, police reports and family members. Analysis included 7,976 road traffic fatalities. Overall, 6,238 (78.2 %) fatalities were male and 2,272 (28.5 %) were children under 18 years of age. The highest numbers of road traffic fatalities were among males 15 to 34 years of age and children of both sexes under 5 years of age. 49.2 % of fatalities occurred among pedestrians. Among children and females, the majority of road traffic fatalities were pedestrians, 69.0 % and 56.6 %, respectively. Fatalities among motorcyclists (3.7 %) and bicyclists (0.4 %) were least common. Rates of road traffic fatalities ranged from 8.6 to 10.7 per 100,000 population. The injury surveillance system provides the first data from a conflict-affected country on road traffic fatalities disaggregated by type of road user. The highest numbers of fatalities were among children and young men. Nearly half of fatalities were pedestrians, a proportion nearly double that of any neighboring country. As insurgency activity increased in 2013, the number of road traffic fatalities declined.

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

PubMed

Logue, Jennifer; Murray, Heather M; Welsh, Paul; Shepherd, James; Packard, Chris; Macfarlane, Peter; Cobbe, Stuart; Ford, Ian; Sattar, Naveed

2011-04-01

The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4 kg/m² as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9 kg/m² in both the minimally adjusted model (HR = 1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR = 1.60 (95% CI 1.02 to 2.53)). These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons.

PubMed

Chan, Jasper Fuk-Woo; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Houshun; Poon, Vincent Kwok-Man; Tee, Kah-Meng; Zhu, Zheng; Cai, Jian-Piao; Tsang, Jessica Oi-Ling; Chik, Kenn Ka-Heng; Yin, Feifei; Chan, Kwok-Hung; Kok, Kin-Hang; Jin, Dong-Yan; Au-Yeung, Rex Kwok-Him; Yuen, Kwok-Yung

2016-12-01

Disseminated or fatal Zika virus (ZIKV) infections were reported in immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse models may not be suitable for evaluating treatment effects of recombinant interferons. We developed a novel mouse model for ZIKV infection by immunosuppressing BALB/c mice with dexamethasone. Dexamethasone-immunosuppressed male mice (6-8weeks) developed disseminated infection as evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in multiple organs. They had ≥10% weight loss and high clinical scores soon after dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral loads in blood and most tissues at 5dpi were significantly higher than those at 12dpi (P<0.05). Histological examination revealed prominent inflammatory infiltrates in multiple organs, and CD45+ and CD8+ inflammatory cells were seen in the testis. These findings suggested that clinical deterioration occurred during viral clearance by host immune response. Type I interferon treatments improved clinical outcome of mice (100% vs 0% survival). Besides virus dissemination, inflammation of various tissues, especially orchitis, may be potential complications of ZIKV infection with significant implications on disease transmission and male fertility. Interferon treatment should be considered in patients at high risks for ZIKV-associated complications when the potential benefits outweigh the side effects of treatment. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of state-level policy changes on homicide and nonfatal shootings of law enforcement officers.

PubMed

Crifasi, Cassandra K; Pollack, Keshia M; Webster, Daniel W

2016-08-01

To evaluate the impact of state-level policy changes on assaults on law enforcement officers (LEOs) in the USA. Pooled time series and cross-sections with negative binomial regression were used to estimate the impact of state-level changes of right-to-carry (RTC), three-strikes and permit-to-purchase (PTP) handgun laws on fatal and non-fatal assaults of LEOs. LEO assaults were stratified by weapon type (all methods, handgun and non-handgun) and whether or not the assault was fatal. Data were collected from the Federal Bureau of Investigation's Law Enforcement Officers Killed and Assaulted database and analysed for the period 1984-2013 for fatal assaults and 1998-2013 for non-fatal assaults. RTC laws showed no association with fatal (p>0.4) or non-fatal (p>0.15) assaults on LEOs. Three-strikes laws were associated with a 33% increase in the risk of fatal assaults on LEOs. Connecticut's PTP law was not associated with fatal (p>0.16) or non-fatal (p>0.13) assaults. Missouri's repeal of its PTP legislation was marginally associated with a twofold increased risk of non-fatal handgun assaults (p=0.089). This research indicates that three-strikes laws increase the risk of fatal assaults. RTC laws are not associated with increased risk of assault. Missouri's PTP repeal may increase the risk of non-fatal handgun assaults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Growth Hormone Deficiency, Brain Development, and Intelligence

ERIC Educational Resources Information Center

Meyer-Bahlburg, Heino F. L.; And Others

1978-01-01

Available from: American Medical Association, 535 N. Dearborn Street, Chicago, Illinois 60610. In order to determine what effect, if any, growth hormone (GH) has on human brain development, 29 patients (mean age 11.7 years) with GH deficiency were selected according to the following criteria: no evidence of reversible GH deficiency, onset of…

Estimated rate of fatal automobile accidents attributable to acute solvent exposure at low inhaled concentrations.

PubMed

Benignus, Vernon A; Bushnell, Philip J; Boyes, William K

2011-12-01

Acute solvent exposures may contribute to automobile accidents because they increase reaction time and decrease attention, in addition to impairing other behaviors. These effects resemble those of ethanol consumption, both with respect to behavioral effects and neurological mechanisms. These observations, along with the extensive data on the relationship between ethanol consumption and fatal automobile accidents, suggested a way to estimate the probability of fatal automobile accidents from solvent inhalation. The problem can be approached using the logic of the algebraic transitive postulate of equality: if A=B and B=C, then A=C. We first calculated a function describing the internal doses of solvent vapors that cause the same magnitude of behavioral impairment as ingestion of ethanol (A=B). Next, we fit a function to data from the literature describing the probability of fatal car crashes for a given internal dose of ethanol (B=C). Finally, we used these two functions to generate a third function to estimate the probability of a fatal car crash for any internal dose of organic solvent vapor (A=C). This latter function showed quantitatively (1) that the likelihood of a fatal car crash is increased by acute exposure to organic solvent vapors at concentrations less than 1.0 ppm, and (2) that this likelihood is similar in magnitude to the probability of developing leukemia from exposure to benzene. This approach could also be applied to other potentially adverse consequences of acute exposure to solvents (e.g., nonfatal car crashes, property damage, and workplace accidents), if appropriate data were available. © 2011 Society for Risk Analysis Published 2011. This article is a U.S. Government work and is in the public domain for the U.S.A.

Impact of earthquake source complexity and land elevation data resolution on tsunami hazard assessment and fatality estimation

NASA Astrophysics Data System (ADS)

Muhammad, Ario; Goda, Katsuichiro

2018-03-01

This study investigates the impact of model complexity in source characterization and digital elevation model (DEM) resolution on the accuracy of tsunami hazard assessment and fatality estimation through a case study in Padang, Indonesia. Two types of earthquake source models, i.e. complex and uniform slip models, are adopted by considering three resolutions of DEMs, i.e. 150 m, 50 m, and 10 m. For each of the three grid resolutions, 300 complex source models are generated using new statistical prediction models of earthquake source parameters developed from extensive finite-fault models of past subduction earthquakes, whilst 100 uniform slip models are constructed with variable fault geometry without slip heterogeneity. The results highlight that significant changes to tsunami hazard and fatality estimates are observed with regard to earthquake source complexity and grid resolution. Coarse resolution (i.e. 150 m) leads to inaccurate tsunami hazard prediction and fatality estimation, whilst 50-m and 10-m resolutions produce similar results. However, velocity and momentum flux are sensitive to the grid resolution and hence, at least 10-m grid resolution needs to be implemented when considering flow-based parameters for tsunami hazard and risk assessments. In addition, the results indicate that the tsunami hazard parameters and fatality number are more sensitive to the complexity of earthquake source characterization than the grid resolution. Thus, the uniform models are not recommended for probabilistic tsunami hazard and risk assessments. Finally, the findings confirm that uncertainties of tsunami hazard level and fatality in terms of depth, velocity and momentum flux can be captured and visualized through the complex source modeling approach. From tsunami risk management perspectives, this indeed creates big data, which are useful for making effective and robust decisions.

Social Integration and Reduced Risk of Coronary Heart Disease in Women: The Role of Lifestyle Behaviors

PubMed Central

Chang, Shun-Chiao; Glymour, Maria; Cornelis, Marilyn; Walter, Stefan; Rimm, Eric B.; Tchetgen, Eric Tchetgen; Kawachi, Ichiro; Kubzansky, Laura D.

2017-01-01

Rationale Higher social integration is associated with lower cardiovascular mortality; however, whether it is associated with incident coronary heart disease (CHD), especially in women, and if associations differ by case fatality is unclear. Objectives This study sought to examine the associations between social integration and risk of incident CHD in a large female prospective cohort. Methods and Results 76,362 women in the Nurses’ Health Study (NHS), free of CHD and stroke at baseline (1992), were followed until 2014. Social integration was assessed by a simplified Berkman-Syme Social Network Index every 4 years. Endpoints included nonfatal myocardial infarction (MI) and fatal CHD. 2,372 incident CHD events occurred throughout follow-up. Adjusting for demographic, health/medical risk factors and depressive symptoms, being socially integrated was significantly associated with lower CHD risk, particularly fatal CHD. The most socially integrated women had a hazard ratio of 0.55 (95% confidence interval, 0.41–0.73) of developing fatal CHD compared to those least socially integrated (p-for-trend < 0.0001). When additionally adjusting for lifestyle behaviors, findings for fatal CHD were maintained but attenuated (p-for-trend = 0.02) whereas the significant associations no longer remained for nonfatal MI. The inverse associations between social integration and nonfatal MI risk were largely explained by health-promoting behaviors, particularly through differences in cigarette smoking; however, the association with fatal CHD risk remained after accounting for these behaviors and thus may involve more direct biological mechanisms. Conclusions Social integration is inversely associated with CHD incidence in women, but is largely explained by lifestyle/behavioral pathways. PMID:28373350

Characteristics of non-fatal abusive head trauma among children in the USA, 2003--2008: application of the CDC operational case definition to national hospital inpatient data.

PubMed

Parks, Sharyn; Sugerman, David; Xu, Likang; Coronado, Victor

2012-12-01

An International Classification of Diseases code-based case definition for non-fatal abusive head trauma (AHT) in children <5 years of age was developed in March 2008 by an expert panel convened at the Centers for Disease Control and Prevention (CDC). This study presents an application of the CDC recommended operational case definition of AHT to US hospital inpatient data to characterise the AHT hospitalisation rate for children <5 years of age. Nationwide Inpatient Sample (NIS) data from the Healthcare Cost and Utilisation Project from 2003 to 2008 were examined. Inspection of the NIS data resulted in the identification of an estimated 10 555 non-fatal AHT hospitalisations with 9595 classified as definite/presumptive AHT and 960 classified as probable AHT. The non-fatal AHT rate was highest among children aged <1 year (32.3 per 100 000) with a peak in hospitalisations between 1 and 3 months of age. Non-fatal AHT hospitalisation rates for children <2 years of age were higher for boys (21.9 per 100 000) than girls (15.3 per 100 000). The non-fatal AHT hospitalisation rate showed little variation across seasons. To reduce the burden of AHT in the USA, a preventable public health problem, concerted prevention efforts targeting populations at risk should be implemented. This report demonstrates a model procedure for using the new CDC definition for public health surveillance and research purposes. Such findings can be used to inform parents and providers about AHT (eg, dangers of shaking, strategies for managing infant crying) as well as to monitor better the impact of prevention strategies over time.

Characteristics of non-fatal abusive head trauma among children in the USA, 2003–2008: application of the CDC operational case definition to national hospital inpatient data

PubMed Central

Parks, Sharyn; Sugerman, David; Xu, Likang; Coronado, Victor

2016-01-01

Objective An International Classification of Diseases code-based case definition for non-fatal abusive head trauma (AHT) in children <5 years of age was developed in March 2008 by an expert panel convened at the Centers for Disease Control and Prevention (CDC). This study presents an application of the CDC recommended operational case definition of AHT to US hospital inpatient data to characterise the AHT hospitalisation rate for children <5 years of age. Methods Nationwide Inpatient Sample (NIS) data from the Healthcare Cost and Utilisation Project from 2003 to 2008 were examined. Results Inspection of the NIS data resulted in the identification of an estimated 10 555 non-fatal AHT hospitalisations with 9595 classified as definite/presumptive AHT and 960 classified as probable AHT. The non-fatal AHT rate was highest among children aged <1 year (32.3 per 100 000) with a peak in hospitalisations between 1 and 3 months of age. Non-fatal AHT hospitalisation rates for children <2 years of age were higher for boys (21.9 per 100 000) than girls (15.3 per 100 000). The non-fatal AHT hospitalisation rate showed little variation across seasons. Conclusions To reduce the burden of AHT in the USA, a preventable public health problem, concerted prevention efforts targeting populations at risk should be implemented. This report demonstrates a model procedure for using the new CDC definition for public health surveillance and research purposes. Such findings can be used to inform parents and providers about AHT (eg, dangers of shaking, strategies for managing infant crying) as well as to monitor better the impact of prevention strategies over time. PMID:22328632

Global trend according to estimated number of occupational accidents and fatal work-related diseases at region and country level.

PubMed

Hämäläinen, Päivi; Leena Saarela, Kaija; Takala, Jukka

2009-01-01

Although occupational accidents and work-related diseases have been of interest for a long time, due to lack of proper recording and notification systems the official numbers of occupational accidents and work-related diseases are missing for many countries. Presently, the demand for effectiveness and an interest in the economic aspects of accidents have increased prevention activities at company and country levels. Occupational accident data of selected countries and of World Health Organization regional divisions together with the global burden of disease were used in estimating global occupational accidents and fatal work-related diseases. The trend of global occupational accidents and work-related diseases is presented at region and country levels. The years 1998, 2001, and 2003 are compared in the case of occupational accidents and the years 2000 and 2002 in the case of work-related diseases. The total number of occupational accidents and fatal work-related diseases has increased, but the fatality rates per 100,000 workers have decreased. There were almost 360,000 fatal occupational accidents in 2003 and almost 2 million fatal work-related diseases in 2002. Every day more than 960,000 workers get hurt because of accidents. Each day 5,330 people die because of work-related diseases. Information on occupational accidents and work-related diseases is needed so that countries may understand better the importance of occupational health and safety at country and company level. Especially companies in developing countries are not familiar with occupational safety and health. Statistical data is essential for accident prevention; it is a starting point for the safety work.

Relationship between pedestrian headform tests and injury and fatality rates in vehicle-to-pedestrian crashes in the United States.

PubMed

Mueller, Becky; Farmer, Charles; Jermakian, Jessica; Zuby, David

2013-11-01

Pedestrian protection evaluations have been developed to encourage vehicle front-end designs that mitigate the consequences of vehicle-to-pedestrian crashes. The European New Car Assessment Program (Euro NCAP) evaluates pedestrian head protection with impacts against vehicle hood, windshield, and A-pillars. The Global Technical Regulation No. 9 (GTR 9), being evaluated for U.S. regulation, limits head protection evaluations to impacts against vehicle hoods. The objective of this study was to compare results from pedestrian head impact testing to the real-world rates of fatal and incapacitating injuries in U.S. pedestrian crashes. Data from police reported pedestrian crashes in 14 states were used to calculate real-world fatal and in- capacitating injury rates for seven 2002-07 small cars. Rates were 2.17-4.04 per 100 pedestrians struck for fatal injuries and 10.45-15.35 for incapacitating injuries. Euro NCAP style pedestrian headform tests were conducted against windshield, A-pillar, and hoods of the study vehicles. When compared with pedestrian injury rates, the vehicles' Euro NCAP scores, ranging 5-10 points, showed strong negative correlations (-0.6) to injury rates, though none were statistically significant. Data from the headform impacts for each of the study vehicles were used to calculate that vehicle's predicted serious injury risk. The predicted risks from both the Euro NCAP and GTR 9 test zones showed high positive correlations with the pedestrian fatal and incapacitating injury rates, though few were statistically significant. Whether vehicle stiffness is evaluated on all components of vehicle front ends (Euro NCAP) or is limited to hoods (GTR 9), softer vehicle components correspond to a lower risk of fatality.

The role of iodine in human growth and development.

PubMed

Zimmermann, Michael B

2011-08-01

Iodine is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. Iodine deficiency is a major public health problem; globally, it is estimated that two billion individuals have an insufficient iodine intake. Although goiter is the most visible sequelae of iodine deficiency, the major impact of hypothyroidism due to iodine deficiency is impaired neurodevelopment, particularly early in life. In the fetal brain, inadequate thyroid hormone impairs myelination, cell migration, differentiation and maturation. Moderate-to-severe iodine deficiency during pregnancy increases rates of spontaneous abortion, reduces birth weight, and increases infant mortality. Offspring of deficient mothers are at high risk for cognitive disability, with cretinism being the most severe manifestation. It remains unclear if development of the offspring is affected by mild maternal iodine deficiency. Moderate-to-severe iodine deficiency during childhood reduces somatic growth. Correction of mild-to-moderate iodine deficiency in primary school aged children improves cognitive and motor function. Iodine prophylaxis of deficient populations with periodic monitoring is an extremely cost effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle. Copyright © 2011 Elsevier Ltd. All rights reserved.

Rabbit Model for Human EBV-Associated Hemophagocytic Syndrome (HPS)

PubMed Central

Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a “starry sky” pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

How do the definitions of urban and rural matter for transportation safety? Re-interpreting transportation fatalities as an outcome of regional development processes.

PubMed

McAndrews, Carolyn; Beyer, Kirsten; Guse, Clare E; Layde, Peter

2016-12-01

Urban and rural places are integrated through economic ties and population flows. Despite their integration, most studies of road safety dichotomize urban and rural places, and studies have consistently demonstrated that rural places are more dangerous for motorists than urban places. Our study investigates whether these findings are sensitive to the definition of urban and rural. We use three different definitions of urban-rural continua to quantify and compare motor vehicle occupant fatality rates per person-trip and person-mile for the state of Wisconsin. The three urban-rural continua are defined by: (1) popular impressions of urban, suburban, and rural places using a system from regional economics; (2) population density; and (3) the intensity of commute flows to core urbanized areas. In this analysis, the three definitions captured different people and places within each continuum level, highlighting rural heterogeneity. Despite this heterogeneity, the three definitions resulted in similar fatality rate gradients, suggesting a potentially latent "rural" characteristic. We then used field observations of urban-rural transects to refine the definitions. When accounting for the presence of higher-density towns and villages in rural places, we found that low-density urban places such as suburbs and exurbs have fatality rates more similar to those in rural places. These findings support the need to understand road safety within the context of regional development processes instead of urban-rural categories. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using the Molecular Classification of Glioblastoma to Inform Personalized Treatment

PubMed Central

Olar, Adriana; Aldape, Kenneth D.

2014-01-01

Glioblastoma is the most common and most aggressive diffuse glioma, associated with short survival and uniformly fatal outcome irrespective of treatment. It is characterized by morphologic, genetic, and gene-expression heterogeneity. The current standard of treatment is maximal surgical resection, followed by radiation, with concurrent and adjuvant chemotherapy. Due to the heterogeneity most tumors develop resistance to treatment and shortly recur. Following recurrence glioblastoma is quickly fatal in the majority of cases. Recent genetic molecular advances have contributed to a better understanding of glioblastoma pathophysiology and disease stratification. In this paper we review the basic glioblastoma pathophysiology with emphasis on clinically relevant genetic molecular alterations and potential targets for further drug development. PMID:24114756

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.

PubMed

la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Duse, Marzia; Malvagia, Sabrina; Lippi, Francesca; Funghini, Silvia; Bianchi, Leila; Della Bona, Maria Luisa; Valleriani, Claudia; Ombrone, Daniela; Moriondo, Maria; Villanelli, Fabio; Speckmann, Carsten; Adams, Stuart; Gaspar, Bobby H; Hershfield, Michael; Santisteban, Ines; Fairbanks, Lynette; Ragusa, Giovanni; Resti, Massimo; de Martino, Maurizio; Guerrini, Renzo; Azzari, Chiara

2013-06-01

Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear. We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life. We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency. The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis. Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Urban Sprawl as a Risk Factor in Motor Vehicle Occupant and Pedestrian Fatalities

PubMed Central

Ewing, Reid; Schieber, Richard A.; Zegeer, Charles V.

2003-01-01

Objectives. We sought to determine the association between urban sprawl and traffic fatalities. Methods. We created a sprawl index by applying principal components analysis to data for 448 US counties in the largest 101 metropolitan areas. Regression analysis was used to determine associations between the index and traffic fatalities. Results. For every 1% increase in the index (i.e., more compact, less sprawl), all-mode traffic fatality rates fell by 1.49% (P < .001) and pedestrian fatality rates fell by 1.47% to 3.56%, after adjustment for pedestrian exposure (P < .001). Conclusions. Urban sprawl was directly related to traffic fatalities and pedestrian fatalities. Subsequent studies should investigate relationships at a finer geographic scale and should strive to improve on the measure of exposure used to adjust pedestrian fatality rates. PMID:12948977

Seat Integrated and Conventional Restraints: A Study of Crash Injury/Fatality Rates in Rollovers

PubMed Central

Padmanaban, Jeya; Burnett, Roger A.

2008-01-01

This study used police-reported motor vehicle crash data from eleven states to determine ejection, fatality, and fatal/serious injury risks for belted drivers in vehicles with conventional seatbelts compared to belted drivers in vehicles with seat integrated restraint systems (SIRS). Risks were compared for 11,159 belted drivers involved in single- or multiple-vehicle rollover crashes. Simple driver ejection (partial and complete), fatality, and injury rates were derived, and logistic regression analyses were used to determine relative contribution of factors (including event calendar year, vehicle age, driver age/gender/alcohol use) that significantly influence the likelihood of fatality and fatal/serious injury to belted drivers in rollovers. Results show no statistically significant difference in driver ejection, fatality, or fatal/serious injury rates between vehicles with conventional belts and vehicles with SIRS. PMID:19026243

NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS

PubMed Central

Fox, John P.

1943-01-01

Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent. The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus. Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies. The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D3), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non-fatal infections, thus, may be important to the accuracy of quantitative determinations of infectivity. Limited observations with virus of the French neurotropic and the pantropic Asibi strains revealed that non-fatal infections do occur, but only rarely. Somewhat more extensive observations with unmodified virus of strains isolated from Brazilian cases of jungle yellow fever, in contrast, revealed an occurrence of non-fatal infections much greater than that observed with the most productive 17D substrains. With these jungle strains, the demonstration of non-fatal infections proved indispensable to any measure of the level of infectivity of virus preparations. The demonstration of the proportional occurrence in mice of non-fatal infections with yellow fever virus provides an additional means by which different virus strains and substrains may be characterized. PMID:19871300

Severe and fatal complications after diagnostic and therapeutic ERCP: a prospective series of claims to insurance covering public hospitals.

PubMed

Trap, R; Adamsen, S; Hart-Hansen, O; Henriksen, M

1999-02-01

Increasing numbers of patients are undergoing endoscopic retrograde cholangiopancreatography (ERCP) prior to laparoscopic cholecystectomy, and more departments and doctors are performing ERCP, while new data from large prospective series have documented the risks of both diagnostic and therapeutic ERCP. The establishment in Denmark of a Patient Insurance Association, which has covered injury caused during investigation and treatment in public hospitals since July 1992, has made it possible to collect and analyze a large prospective series of ERCP complications for which compensation has been claimed. Thirty-nine consecutive claims for compensation due to complications after ERCP occurring between 1 July 1992 and 31 December 1996 were investigated. Case notes were reviewed, along with laboratory reports and radiographs. The complications were classified according to the international consensus. Claims for compensation were made in 39 cases from 25 hospitals. The indication for ERCP was appropriate in 31. Precut papillotomy for access had been performed in seven. The severity of the complications was mild in one patient, moderate in three patients, severe in 24, and fatal in nine; in two cases, the severity was not classifiable. The complications were: pancreatitis in 23 patients (seven cases fatal, one of which had involved a precut procedure), bleeding in two, perforation in nine (six had a precut procedure, one died), and other reasons in five (including one fatal case). Among the nine fatal cases, cannulation had not been achieved in two and the endoscopic retrograde cholangiogram was normal in four, one of whom underwent a sphincterotomy. One patient with a previous adenoma had an endoprosthesis removed, developed gangrenous cholecystitis afterward, and died. Thirty patients were eligible for compensation. The rejected cases included mild and moderate pancreatitis, a case of fatal hemorrhagic pancreatitis in which the patient had refused blood transfusion, and one patient who had pancreatitis prior to ERCP. ERCP, even for diagnostic purposes, may be associated with very serious and even fatal complications. The use of the precut procedure for access should still be considered dangerous. Other means of investigating the bile ducts should be developed. If endoscopic ultrasonography and magnetic resonance cholangiography prove to have the same diagnostic value as ERCP, which must be considered the gold standard for visualizing the ducts today, they might replace ERCP as the primary investigation in patients with an intermediate or low risk of bile duct stones; this would reduce the numbers of patients exposed to the risks of ERCP.

Case-Based Teaching of Fatal Incidents in Outdoor Education Teacher Preparation Courses

ERIC Educational Resources Information Center

North, Chris; Brookes, Andrew

2017-01-01

This article examines the use of case-based approaches to fatal incidents in outdoor education (OE) with a view to fatality prevention. Fatalities are rare in OE and therefore it is nearly impossible for teachers to learn how to avoid fatalities from their own past experiences. It is, however, possible to learn from the mistakes of others through…

US Traffic Fatalities, 1985–2014, and Their Relationship to Medical Marijuana Laws

PubMed Central

Mauro, Christine M.; Wall, Melanie M.; Kim, June H.; Cerdá, Magdalena; Keyes, Katherine M.; Hasin, Deborah S.; Galea, Sandro; Martins, Silvia S.

2017-01-01

Objectives. To determine the association of medical marijuana laws (MMLs) with traffic fatality rates. Methods. Using data from the 1985–2014 Fatality Analysis Reporting System, we examined the association between MMLs and traffic fatalities in multilevel regression models while controlling for contemporaneous secular trends. We examined this association separately for each state enacting MMLs. We also evaluated the association between marijuana dispensaries and traffic fatalities. Results. On average, MML states had lower traffic fatality rates than non-MML states. Medical marijuana laws were associated with immediate reductions in traffic fatalities in those aged 15 to 24 and 25 to 44 years, and with additional yearly gradual reductions in those aged 25 to 44 years. However, state-specific results showed that only 7 states experienced post-MML reductions. Dispensaries were also associated with traffic fatality reductions in those aged 25 to 44 years. Conclusions. Both MMLs and dispensaries were associated with reductions in traffic fatalities, especially among those aged 25 to 44 years. State-specific analysis showed heterogeneity of the MML–traffic fatalities association, suggesting moderation by other local factors. These findings could influence policy decisions on the enactment or repealing of MMLs and how they are implemented. PMID:27997245

Automobile driver fatalities in frontal impacts: air bags compared with manual belts.

PubMed Central

Zador, P L; Ciccone, M A

1993-01-01

OBJECTIVES. The effectiveness of air bags was estimated in this study by comparing driver fatalities in frontal crashes with driver fatalities in nonfrontal crashes, for cars with air bags and manual belts and cars with manual belts only. METHODS. Fatal Accident Reporting System data for drivers fatally injured during 1985 to 1991 in 1985 to 1991 model year cars that were equipped with air bags in or before model year 1991 were analyzed. RESULTS. Driver fatalities in frontal crashes in air bag cars were 28% lower than those in comparable cars with manual belts only. This percentage was used for estimating the overall fatality reduction in air bag cars. The reduction was greater in large cars (50%) than in midsize cars (19%) or in small cars (14%). Air bags reduced driver fatalities in frontal crashes involving ejection by about 9%. Fatalities in frontal crashes among drivers who were reportedly using manual belts at the time of the crash were reduced by about 15%. The comparable reduction among drivers who were reportedly not using manual belts was 31%. CONCLUSION. It was estimated that air bags reduced the total number of all driver fatalities by about 19%. PMID:8484445

Trends in Fatalities From Distracted Driving in the United States, 1999 to 2008

PubMed Central

Stimpson, Jim P.

2010-01-01

Objectives. We examined trends in distracted driving fatalities and their relation to cell phone use and texting volume. Methods. The Fatality Analysis Reporting System (FARS) records data on all road fatalities that occurred on public roads in the United States from 1999 to 2008. We studied trends in distracted driving fatalities, driver and crash characteristics, and trends in cell phone use and texting volume. We used multivariate regression analysis to estimate the relation between state-level distracted driving fatalities and texting volumes. Results. After declining from 1999 to 2005, fatalities from distracted driving increased 28% after 2005, rising from 4572 fatalities to 5870 in 2008. Crashes increasingly involved male drivers driving alone in collisions with roadside obstructions in urban areas. By use of multivariate analyses, we predicted that increasing texting volumes resulted in more than 16 000 additional road fatalities from 2001 to 2007. Conclusions. Distracted driving is a growing public safety hazard. Specifically, the dramatic rise in texting volume since 2005 appeared to be contributing to an alarming rise in distracted driving fatalities. Legislation enacting texting bans should be paired with effective enforcement to deter drivers from using cell phones while driving. PMID:20864709

Trends in fatalities from distracted driving in the United States, 1999 to 2008.

PubMed

Wilson, Fernando A; Stimpson, Jim P

2010-11-01

We examined trends in distracted driving fatalities and their relation to cell phone use and texting volume. The Fatality Analysis Reporting System (FARS) records data on all road fatalities that occurred on public roads in the United States from 1999 to 2008. We studied trends in distracted driving fatalities, driver and crash characteristics, and trends in cell phone use and texting volume. We used multivariate regression analysis to estimate the relation between state-level distracted driving fatalities and texting volumes. After declining from 1999 to 2005, fatalities from distracted driving increased 28% after 2005, rising from 4572 fatalities to 5870 in 2008. Crashes increasingly involved male drivers driving alone in collisions with roadside obstructions in urban areas. By use of multivariate analyses, we predicted that increasing texting volumes resulted in more than 16,000 additional road fatalities from 2001 to 2007. Distracted driving is a growing public safety hazard. Specifically, the dramatic rise in texting volume since 2005 appeared to be contributing to an alarming rise in distracted driving fatalities. Legislation enacting texting bans should be paired with effective enforcement to deter drivers from using cell phones while driving.

Unique fatality due to claw injuries in a tiger attack: a case report.

PubMed

Pathak, Hrishikesh; Dixit, Pradeep; Dhawane, Shailendra; Meshram, Satin; Shrigiriwar, Manish; Dingre, Niraj

2014-11-01

This paper describes a unique case of a fatal tiger attack in the wild. In the present case, a tiger fatally mauled a 34-year-old female with its claws, instead of the usual mechanism of killing by the bite injury to the neck. The autopsy revealed multiple fatal and non-fatal injuries caused by the tiger claws. The characteristic injuries due to the tooth impacts were absent as the teeth of the offending tiger were either fallen or non-functional. To the best of our knowledge, probably this rare case would be the first reported human fatality due to the tiger claw injuries in the world. The purpose of the present article is to highlight the fatal injuries due to the tiger claws, as the claw-induced fatal injuries in a tiger attack are not reported in the medico-legal literature. Moreover, this report would be an illustrative one for differentiation between the fatal injuries due to the claws and tooth impacts in a tiger attack. Furthermore, the present report establishes the importance of the tiger claws as a source of fatal injuries in a tiger attack. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Fatal and Non-Fatal Overdose After Narcology Hospital Discharge Among Russians Living with HIV/Aids who Inject Drugs‡

PubMed Central

Walley, Alexander Y; Cheng, Debbie M; Quinn, Emily K.; Blokhina, Elena; Gnatienko, Natalia; Chaisson, Christine E.; Krupitsky, Evgeny; Coffin, Philip O; Samet, Jeffrey H

2016-01-01

Objectives Among Russians living with HIV/AIDS who inject drugs, we examined the incidence of fatal and non-fatal overdoses following discharge from a narcology hospital and the associations with more advanced HIV infection. Design Prospective cohort study of data collected at baseline, 3 and 6 months from HIV-infected patients with a history of injection drug use who were not treated with anti-retroviral therapy. Participants were recruited between 2012-14 from a narcology (addiction) hospital in St. Petersburg, Russia. Methods Fatal overdose was determined based on contact reports to study staff in the year after discharge. Non-fatal overdose was self-reported at the 3- and 6-month assessments. The main independent variable for HIV severity was CD4 cell count at the baseline interview (<200 cells/mm3 ≥ 200 cells/mm3). Secondary analyses assessed time since HIV diagnosis and treated with anti-retroviral treatment (ART) prior to enrollment as independent variables. We fit Cox proportional hazards models to assess whether HIV severity is associated with either fatal or non-fatal overdose. Results Among 349 narcology patients, 18 participants died from overdose within one year after discharge (8.7%, 95%CI 3.4-14.2 by Kaplan-Meier); an estimated 51% [95% CI 34-68%] reported at least one non-fatal overdose within 6 months of discharge. HIV severity, time since HIV diagnosis and ever ART were not significantly associated with either fatal or non-fatal overdose events. Conclusion Fatal and non-fatal overdose are common among Russians living with HIV/AIDS who inject drugs after narcology hospital discharge. Overdose prevention interventions are urgently warranted among Russian narcology patients with HIV infection. PMID:27907848

Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis.

PubMed

Romualdo, Guilherme Ribeiro; Goto, Renata Leme; Henrique Fernandes, Ana Angélica; Cogliati, Bruno; Barbisan, Luis Fernando

2016-10-01

Although there is a concomitance of zinc deficiency and high incidence/mortality for hepatocellular carcinoma in certain human populations, there are no experimental studies investigating the modifying effects of zinc on hepatocarcinogenesis. Thus, we evaluated whether dietary zinc deficiency or supplementation alter the development of hepatocellular preneoplastic lesions (PNL). Therefore, neonatal male Balb/C mice were submitted to a diethylnitrosamine/2-acetylaminefluorene-induced hepatocarcinogenesis model. Moreover, mice were fed adequate (35 mg/kg diet), deficient (3 mg/kg) or supplemented (180 mg/kg) zinc diets. Mice were euthanized at 12 (early time-point) or 24 weeks (late time-point) after introducing the diets. At the early time-point, zinc deficiency decreased Nrf2 protein expression and GSH levels while increased p65 and p53 protein expression and the number of PNL/area. At the late time-point, zinc deficiency also decreased GSH levels while increased liver genotoxicity, cell proliferation into PNL and PNL size. In contrast, zinc supplementation increased antioxidant defense at both time-points but not altered PNL development. Our findings are the first to suggest that zinc deficiency predisposes mice to the PNL development in chemically-induced hepatocarcinogenesis. The decrease of Nrf2/GSH pathway and increase of liver genotoxicity, as well as the increase of p65/cell proliferation, are potential mechanisms to this zinc deficiency-mediated effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Epidemiology of Drowning in Bangladesh: An Update.

PubMed

Rahman, Aminur; Alonge, Olakunle; Bhuiyan, Al-Amin; Agrawal, Priyanka; Salam, Shumona Sharmin; Talab, Abu; Rahman, Qazi Sadeq-Ur; Hyder, Adnan A

2017-05-05

Over one-quarter of deaths among 1-4 year-olds in Bangladesh were due to drowning in 2003, and the proportion increased to 42% in 2011. This study describes the current burden and risk factors for drowning across all demographics in rural Bangladesh. A household survey was carried out in 51 union parishads of rural Bangladesh between June and November 2013, covering 1.17 million individuals. Information on fatal and nonfatal drowning events was collected by face-to-face interviews using a structured questionnaire. Fatal and non-fatal drowning rates were 15.8/100,000/year and 318.4/100,000/6 months, respectively, for all age groups. The highest rates of fatal (121.5/100,000/year) and non-fatal (3057.7/100,000/6 months) drowning were observed among children 1 to 4 years of age. These children had higher rates of fatal (13 times) and non-fatal drowning (16 times) compared with infants. Males had slightly higher rates of both fatal and non-fatal drowning. Individuals with no education had 3 times higher rates of non-fatal drowning compared with those with high school or higher education. Non-fatal drowning rates increased significantly with decrease in socio-economic status (SES) quintiles, from the highest to the lowest. Drowning is a major public health issue in Bangladesh, and is now a major threat to child survival.

Assessing the impact of Syrian refugees on earthquake fatality estimations in southeast Turkey

NASA Astrophysics Data System (ADS)

Wilson, Bradley; Paradise, Thomas

2018-01-01

The influx of millions of Syrian refugees into Turkey has rapidly changed the population distribution along the Dead Sea Rift and East Anatolian fault zones. In contrast to other countries in the Middle East where refugees are accommodated in camp environments, the majority of displaced individuals in Turkey are integrated into local cities, towns, and villages - placing stress on urban settings and increasing potential exposure to strong earthquake shaking. Yet displaced populations are often unaccounted for in the census-based population models used in earthquake fatality estimations. This study creates a minimally modeled refugee gridded population model and analyzes its impact on semi-empirical fatality estimations across southeast Turkey. Daytime and nighttime fatality estimates were produced for five fault segments at earthquake magnitudes 5.8, 6.4, and 7.0. Baseline fatality estimates calculated from census-based population estimates for the study area varied in scale from tens to thousands of fatalities, with higher death totals in nighttime scenarios. Refugee fatality estimations were analyzed across 500 semi-random building occupancy distributions. Median fatality estimates for refugee populations added non-negligible contributions to earthquake fatalities at four of five fault locations, increasing total fatality estimates by 7-27 %. These findings communicate the necessity of incorporating refugee statistics into earthquake fatality estimations in southeast Turkey and the ongoing importance of placing environmental hazards in their appropriate regional and temporal context.

1990 traffic fatalities : semiannual report

DOT National Transportation Integrated Search

1990-11-01

Author's abstract: This report contains preliminary estimates of traffic fatalities and fatal accidents for the first six months of 1990. Trend data are presented for both the long and short term. The national estimates of fatalities are quite extens...

A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease.

PubMed

Sarathy, Vanessa V; White, Mellodee; Li, Li; Gorder, Summer R; Pyles, Richard B; Campbell, Gerald A; Milligan, Gregg N; Bourne, Nigel; Barrett, Alan D T

2015-01-15

The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Posterior reversible encephalopathy syndrome: Report of a fatal case and analysis of predictive factors of a poor prognosis].

PubMed

Torres, Moisés Ulises; Delgado, Ligia Victoria; Giraldo, Natalia; Urueña, Piedad; Franco, Sergio; Hernández, Olga Helena

2017-04-01

Posterior reversible encephalopathy syndrome is an illness with multiple causes and distinctive clinicalradiological characteristics that should be known by intensivists and emergency room physicians for a timely diagnosis and treatment. A fatal case of posterior reversible encephalopathy syndrome is presented, and the risk factors related to the outcome are identified.A 60-year-old man without a relevant medical history arrived at the emergency room presenting with depressed consciousness, seizures, and high blood pressure. Tomographic images revealed a posterior cerebellar hematoma. Resonance images showed ischemic zones, vasogenic edema from the thalamus to the brain stem, middle cerebellar peduncles, deep white matter of the cerebral hemispheres, and zones of hemorrhagic transformation. Despite medical-surgical management, the patient died. The risk factors described as the cause of the fatal outcome were identified. This case demonstrates that posterior reversible encephalopathy syndrome can occur without triggering risk factors and highlights the need for early recognition to establish an appropriate intervention to avoid injury or a fatal outcome. Cases of posterior reversible encephalopathy syndrome provide opportunities to investigate the susceptibility for the development of this condition and to establish appropriate preventive measures.

"Big Momma Had Sugar, Imma Have It Too" Medical Fatalism and the Language of Faith Among African-American Women in Memphis.

PubMed

Hotz, Kendra G

2015-12-01

This essay offers a theological exploration of the relationship between medical fatalism and religious belonging among African-American women in Memphis. Drawing on the work of black and womanist theologians and on conversations with participants in a diabetes intervention program administered by a faith-based community health provider, I argue that how we narrate the meanings of our bodies is irreducibly religious. The language we use to interpret and communicate the meaning of our bodily existence emerges from a set of assumptions, often unarticulated, about what is of ultimate value to us. The essay focuses on three interlocking features that link faith with fatalism or hope: (1) The idea that if "I don't claim that" disease cannot enter my body; (2) the role of faith-based clinics in re-establishing trust with marginalized communities; and (3) how nuanced attention to the social location of health seekers can re-frame our understanding of patient compliance. Disrupting fatalism can only be done from within a health seeker's own narrative, and therefore, healthcare providers who learn these narratives and respect their holiness will develop more effective interventions.

Identification of differences between rural and urban safety cultures.

PubMed

Rakauskas, Michael E; Ward, Nicholas J; Gerberich, Susan G

2009-09-01

The prevailing risk of traffic fatalities is much larger in rural areas compared to urban areas. A number of explanations have been offered to explain this including road design, emergency medical service proximity, and human factors. This research explored the potential contribution of rural driver attitudes that may underlie the increased fatal crash risk in rural environments. This analysis examined differences between rural and urban drivers in terms of self-reported risk taking for driving behaviors associated with fatal crashes and attitudes toward safety interventions using a large-scale survey. The results suggested that rural drivers engage in riskier behavior, such as not wearing seatbelts, because they have lower perceptions of the risks associated with such behaviors. Results also suggested that vehicle type (e.g., pickup trucks versus passenger vehicles) may be related to seatbelt compliance and frequency of driving under the influence of alcohol. Rural drivers perceived the utility of government-sponsored traffic safety interventions to be lower than their urban counterparts. This study provides insights into the role of the human factor in rural fatal crashes and provides policy suggestions for developing safety interventions that are designed with respect to the psychosocial factors that define the rural culture.

Overview of bureau research directed towards surface powered haulage safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

May, J.P.; Aldinger, J.A.

1995-12-31

Surface mining operations, including mills and preparation plants, employ over 260,000 people. This represents a significant contribution to our nation`s economy and an important source of skilled and well-paying jobs. As mine production has shifted from underground to surface, and with continuing advances in underground mine safety, surface mining has unfortunately become the leader in mine fatalities. In 1994 surface mining accidents accounted for 49% of all mine fatalities, followed by underground mining with 37% and mills and preparation plants with 14%. The U.S. Bureau of Mines (USBM) has targeted surface mining as an important research priority to reduce themore » social and economic costs associated with fatalities and lost-work-time injuries. USBM safety research focuses on the development of technologies that can enhance productivity and reduce mining costs through a reduction in the number and severity of mining accidents. This report summarizes a number of completed and ongoing research programs directed towards surface powered haulage--the single largest category of fatalities in surface mining and a major cause of lost workdays. Research products designed for industry are highlighted and future USBM surface mining safety research is discussed.« less

Fatal Human Case of Zika and Chikungunya Virus Co-Infection with Prolonged Viremia and Viruria.

PubMed

Silva, Kelly R; Bica, Blanca E R G; Pimenta, Eduardo S; Serafim, Rodrigo B; Abreu, Mirhelen M; Gonçalves, Jorge L S; Santana, Larissa de S; Cabral-Castro, Mauro J; Peralta, José M; Cavalcanti, Marta G

2018-06-21

Zika virus (ZIKV) infection usually presents as a mild and self-limited illness, but it may be associated with severe outcomes. We describe a case of a 30-year-old man with systemic erythematous lupus and common variable immunodeficiency who became infected with both Zika (ZIKV) and Chikungunya (CHIKV) virus during the 2016 outbreak in Rio de Janeiro, Brazil. The patient presented with intense wrist and right ankle arthritis, and ZIKV RNA and virus particles were detected in synovial tissue, blood and urine, and CHIKV RNA in serum sample, at the time of the diagnosis. During the follow up, ZIKV RNA persisted for 275 days post symptoms onset. The patient evolved with severe arthralgia/arthritis and progressive deterioration of renal function. Fatal outcome occurred after 310 days post ZIKV and CHIKV co-infection onset. The results show the development of severe disease and fatal outcome of ZIKV infection in an immunosuppressed adult. The data suggests a correlation between immunodeficiency and prolonged ZIKV RNA shedding in both blood and urine with progressive disease. The results also indicate a possible role for arbovirus co-infections as risk factors for severe and fatal outcomes from ZIKV infection.

Fatal falls and PFAS use in the construction industry: Findings from the NIOSH FACE reports.

PubMed

Dong, Xiuwen Sue; Largay, Julie A; Choi, Sang D; Wang, Xuanwen; Cain, Chris Trahan; Romano, Nancy

2017-05-01

This study analyzed the Construction FACE Database (CFD), a quantitative database developed from reports of the Fatality Assessment and Control Evaluation (FACE) program conducted by the National Institute for Occupational Safety and Health (NIOSH). The CFD contains detailed data on 768 fatalities in the construction industry reported by NIOSH and individual states from 1982 through June 30, 2015. The results show that falls accounted for 42% (325) of the 768 fatalities included in the CFD. Personal fall arrest systems (PFAS) were not available to more than half of the fall decedents (54%); nearly one in four fall decedents (23%) had access to PFAS, but were not using it at the time of the fall. Lack of access to PFAS was particularly high among residential building contractors as well as roofing, siding, and sheet metal industry sectors (∼70%). Although the findings may not represent the entire construction industry today, they do provide strong evidence in favor of fall protection requirements by the Occupational Safety and Health Administration (OSHA). In addition to stronger enforcement, educating employers and workers about the importance and effectiveness of fall protection is crucial for compliance and fall prevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fatal falls and PFAS use in the construction industry: Findings from the NIOSH FACE reports

PubMed Central

Dong, Xiuwen Sue; Largay, Julie A.; Choi, Sang D.; Wang, Xuanwen; Cain, Chris Trahan; Romano, Nancy

2017-01-01

This study analyzed the Construction FACE Database (CFD), a quantitative database developed from reports of the Fatality Assessment and Control Evaluation (FACE) program conducted by the National Institute for Occupational Safety and Health (NIOSH). The CFD contains detailed data on 768 fatalities in the construction industry reported by NIOSH and individual states from 1982 through June 30, 2015. The results show that falls accounted for 42% (325) of the 768 fatalities included in the CFD. Personal fall arrest systems (PFAS) were not available to more than half of the fall decedents (54%); nearly one in four fall decedents (23%) had access to PFAS, but were not using it at the time of the fall. Lack of access to PFAS was particularly high among residential building contractors as well as roofing, siding, and sheet metal industry sectors (~70%). Although the findings may not represent the entire construction industry today, they do provide strong evidence in favor of fall protection requirements by the Occupational Safety and Health Administration (OSHA). In addition to stronger enforcement, educating employers and workers about the importance and effectiveness of fall protection is crucial for compliance and fall prevention. PMID:28292698

Fatal interstitial lung disease associated with icotinib.

PubMed

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi; Chen, Rongchang

2014-12-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment.

Fatal interstitial lung disease associated with icotinib

PubMed Central

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi

2014-01-01

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment. PMID:25590006

Recent trends in cyclist fatalities in Australia.

PubMed

Boufous, Soufiane; Olivier, Jake

2016-08-01

The study examines trends in bicycling fatalities reported to the Australian police between 1991 and 2013. Trends were estimated using Poisson regression modelling. Overall, cycling fatalities decreased by 1.9% annually between 1991 and 2013. However, while deaths following multivehicle crashes decreased at a rate of 2.9% per annum (95% CI -4.0% to -1.8%), deaths from single vehicle crashes increased by 5.8% per annum (95% CI 4.1% to 7.5%). Over the study period, the average age of cyclists who died in single vehicle crashes (45.3 years, 95% CI 41.5 to 49.1) was significantly higher than cyclists who died in multivehicle crashes (36.2 years, 95% CI 34.7 to 37.7). The average age of deceased cyclists increased significantly for both types of crashes. The observed increase in single vehicle crashes need to be closely monitored in Australia and internationally. In-depth studies are needed to investigate the circumstances of fatal single bicycle crashes in order to develop appropriate countermeasures. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Treatment Development of Triheptanoin (G1D)

ClinicalTrials.gov

2018-06-20

Epilepsy; GLUT1DS1; Glut1 Deficiency Syndrome 1, Autosomal Recessive; Glucose Metabolism Disorders; Glucose Transport Defect; Glucose Transporter Type 1 Deficiency Syndrome; Glucose Transporter Protein Type 1 Deficiency Syndrome

The PMMA epidemic in Norway: comparison of fatal and non-fatal intoxications.

PubMed

Vevelstad, Merete; Øiestad, Elisabeth Leere; Middelkoop, Gerrit; Hasvold, Inger; Lilleng, Peer; Delaveris, Gerd Jorunn M; Eggen, Tormod; Mørland, Jørg; Arnestad, Marianne

2012-06-10

During a 6 month period (July 2010-January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as "Death", is occasionally found in street drugs offered as "ecstasy" or "amphetamine". The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15-50) with 67% males; in non-fatal cases 27 years (20-47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17-3.30), which is in the reported lethal range of 0.6-3.1 mg/L in peripheral blood and 1.2-15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01-0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58-3.30), 2.56 (1.52-3.23) and 0.52 mg/L (0.17-1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal "ecstasy" or "speed" drugs. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Association of Graduated Driver Licensing With Driver, Non-Driver, and Total Fatalities Among Adolescents.

PubMed

Zhu, Motao; Zhao, Songzhu; Long, D Leann; Curry, Allison E

2016-07-01

Graduated driver licensing systems typically require an extended learner permit phase, and create night-time driving or passenger restrictions for adolescent drivers. Restricted driving might increase the use of alternative transportation to replace driving and consequently increase crashes and injuries for passengers, bus riders, pedestrians, and bicyclists. This study examined whether graduated driver licensing increases non-driver fatalities among adolescents, and whether it reduces total traffic fatalities combining drivers and non-drivers. Longitudinal analyses were conducted using data from the 1995-2012 U.S. Fatality Analysis Reporting System. Adjusted rate ratios were estimated for being fatally injured in a crash according to: (1) presence/absence of a graduated driver licensing system; and (2) four levels of graduated driver licensing systems (absent, weak, medium, strong). Analyses were conducted in 2015. Among adolescents aged 16 years, graduated driver licensing was not associated with increased passenger fatalities (adjusted rate ratio, 0.96; 95% CI=0.90, 1.03) or pedestrian and bicyclist fatalities (adjusted rate ratio, 1.09; 95% CI=0.85, 1.39), but was associated with an 11% reduction in total traffic fatalities. Among those aged 17 years, graduated driver licensing was not associated with increased fatalities as passengers, pedestrians, or bicyclists, and was not associated with reduced total traffic fatalities. In general, graduated driver licensing systems were not associated with increased fatalities as passengers, pedestrians, bicyclists, and bus riders. Graduated driver licensing systems were associated with reduced total fatalities of adolescents aged 16 years. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia.

PubMed

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert; Gessler, Manfred

2017-10-01

TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.

TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia

PubMed Central

Wegert, Jenny; Vokuhl, Christian; Ziegler, Barbara; Ernestus, Karen; Leuschner, Ivo; Furtwängler, Rhoikos; Graf, Norbert

2017-01-01

Abstract TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non‐fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II–IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non‐anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non‐anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high‐risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease. PMID:29085664

Neglecting safety precautions may lead to trenching fatalities.

PubMed

Deatherage, J Harold; Furches, Lisa K; Radcliffe, Mike; Schriver, William R; Wagner, John P

2004-06-01

Trench collapses ranked as the seventh leading cause of the possible twenty-nine causes of OSHA-inspected fatal construction events during the period 1991-2001. This study aims to examine why these fatalities occurred. Forty-four case files from OSHA inspections of fatal trench collapses were reviewed. Improper protection of the excavation site where work was taking place was the leading fatality cause. Several organizational or physical conditions were present at many fatal sites; the most frequent was that no training had been provided for trenching. Presence of a competent, diligent person at the site would have prohibited most fatalities. The top cited violation was lack of protection, that is, benching, shoring, sloping, trench boxes, etc. (29 CFR 1926.652 (a) (1)). Copyright 2004 Wiley-Liss, Inc.

Exploring the risk factors associated with the size and severity of roadway crashes in Riyadh.

PubMed

Hassan, Hany M; Al-Faleh, Hesham

2013-12-01

Recently, growing concern has been shifting toward the necessity of improving traffic safety in the Kingdom of Saudi Arabia (KSA). KSA has a unique traffic safety problem in that: (a) it can be classified as a developed country in terms of the magnitude and quality of the roadway networks available and its compatibility with international standards; however, (b) it can also be considered a developing country as the rate of increase in the number of road crashes is substantial compared with relevant figures of other developing countries and other countries of the Gulf region. Hence, more research efforts are still needed. This paper examines the nature and causes of fatal and serious traffic crashes in KSA so that solutions and/or future studies can be suggested. Data from 11,545 reported fatal and injury traffic crashes that occurred in Riyadh (the capital of KSA) during the period 2004-2011 were analyzed by alternative and complementary methods. A logistic regression model was estimated and the results revealed that crash reason (speeding), damages in public property, day of the week, crash location (non-intersection location), and point of collision (head-on) were the significant variables affecting the binary target variable (fatal and non-fatal crashes). Additionally, the structural equation modeling approach was developed to identify and quantify the impacts of significant variables influencing crash size (e.g., no. of injuries, no. of vehicles involved in the crash). Crash size is one of the important indices that measure the level of safety of transportation facilities. The results showed that road factor was the most significant factor affecting the size of the crash followed by the driver and environment factors. Considering the results of this study, practical suggestions on how to improve traffic safety in KSA are also presented and discussed. © 2013.

Analysis of Ejection in Fatal Crashes

DOT National Transportation Integrated Search

1997-11-01

Data from NHTSA's Fatality Analysis Reporting System (FARS) show that the : ejection rate among fatally injured passenger vehicle occupants has remained at : over 20 percent since the early 1980's. Because the risk of fatality in a crash : is over th...

Traffic safety facts 1999 : state traffic data

DOT National Transportation Integrated Search

2000-01-01

This traffic safety fact sheet presents state traffic data in a figure showing 1999 Traffic Fatalities by State and Percent Change from 1998 and in 11 tables showing: (1) Traffic Fatalities and Fatality Rates, 1999; (2) Traffic Fatalities and Percent...

Traffic safety facts 1998 : state traffic data

DOT National Transportation Integrated Search

1999-01-01

This publication contains a map of the United States showing 1998 traffic fatalities by state and percent change from 1997 and eleven tables containing data on the following: (1) Traffic fatalities and fatality rates, 1998; (2) Traffic fatalities and...

fatalityCMR: capture-recapture software to correct raw counts of wildlife fatalities using trial experiments for carcass detection probability and persistence time

USGS Publications Warehouse

Peron, Guillaume; Hines, James E.

2014-01-01

Many industrial and agricultural activities involve wildlife fatalities by collision, poisoning or other involuntary harvest: wind turbines, highway network, utility network, tall structures, pesticides, etc. Impacted wildlife may benefit from official protection, including the requirement to monitor the impact. Carcass counts can often be conducted to quantify the number of fatalities, but they need to be corrected for carcass persistence time (removal by scavengers and decay) and detection probability (searcher efficiency). In this article we introduce a new piece of software that fits a superpopulation capture-recapture model to raw count data. It uses trial data to estimate detection and daily persistence probabilities. A recurrent issue is that fatalities of rare, protected species are infrequent, in which case the software offers the option to switch to an ‘evidence of absence’ mode, i.e., estimate the number of carcasses that may have been missed by field crews. The software allows distinguishing between different turbine types (e.g. different vegetation cover under turbines, or different technical properties), as well between two carcass age-classes or states, with transition between those classes (e.g, fresh and dry). There is a data simulation capacity that may be used at the planning stage to optimize sampling design. Resulting mortality estimates can be used 1) to quantify the required amount of compensation, 2) inform mortality projections for proposed development sites, and 3) inform decisions about management of existing sites.

An investigation on fatality of drivers in vehicle-fixed object accidents on expressways in China: Using multinomial logistic regression model.

PubMed

Peng, Yong; Peng, Shuangling; Wang, Xinghua; Tan, Shiyang

2018-06-01

This study aims to identify the effects of characteristics of vehicle, roadway, driver, and environment on fatality of drivers in vehicle-fixed object accidents on expressways in Changsha-Zhuzhou-Xiangtan district of Hunan province in China by developing multinomial logistic regression models. For this purpose, 121 vehicle-fixed object accidents from 2011-2017 are included in the modeling process. First, descriptive statistical analysis is made to understand the main characteristics of the vehicle-fixed object crashes. Then, 19 explanatory variables are selected, and correlation analysis of each two variables is conducted to choose the variables to be concluded. Finally, five multinomial logistic regression models including different independent variables are compared, and the model with best fitting and prediction capability is chosen as the final model. The results showed that the turning direction in avoiding fixed objects raised the possibility that drivers would die. About 64% of drivers died in the accident were found being ejected out of the car, of which 50% did not use a seatbelt before the fatal accidents. Drivers are likely to die when they encounter bad weather on the expressway. Drivers with less than 10 years of driving experience are more likely to die in these accidents. Fatigue or distracted driving is also a significant factor in fatality of drivers. Findings from this research provide an insight into reducing fatality of drivers in vehicle-fixed object accidents.

News reports of bullying-related fatal and nonfatal injuries in the Americas.

PubMed

Srabstein, Jorge Carlos

2013-05-01

Bullying is a multifaceted and injurious form of maltreatment, prevalent across social settings and around the globe. Victims and perpetrators of bullying are at significant risk of suffering from an array of morbidity and dying young due to accidental injuries, suicide, and homicide. This study reviews news reports of nonfatal and fatal injuries linked to bullying throughout the Western Hemisphere during 12 months. News reports, obtained through a Google search, of episodes of fatal and nonfatal injuries related to school bullying and violence from July 2011 through June 2012 that affected children and adolescents (ages 5 to 19 years) throughout the Americas were analyzed. News reports were found of 82 cases of bullying-related fatal and nonfatal injuries, occurring in one year, across 24 countries and dependent territories in the Western Hemisphere, which have a combined total youth population of 225.5 million children and adolescents ages 5 to 19 years. Ninety-seven percent of the victims were between 10 and 19 years old; 60% of them were below age 15, with a male/female ratio of 2:1. News reports of fatal and nonfatal injurious events related to bullying and affecting children and adolescents in the Americas in one year represent the tip of the public health iceberg composing the unknown magnitude of injuries associated with this type of maltreatment. Data on the magnitude of mortality linked to bullying, which would be of the essence in developing public health policies for its prevention, have not been documented.

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

A small nonhuman primate model for filovirus-induced disease.

PubMed

Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L

2011-11-25

Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Copyright © 2011 Elsevier Inc. All rights reserved.

Role of micronutrients for physical growth and mental development.

PubMed

Singh, Meharban

2004-01-01

Due to control of florid and severe cases of protein-energy malnutrition, deficiencies of micronutrients in children have assumed public health importance. According to National Nutrition Monitoring Bureau of India, over 50% of apparently healthy looking children have subclinical or biochemical deficiencies of vitamin A, vitamins B2, B6, folate and vitamin C. Over two-third of children have clinical evidences of iron deficiency while deficiency of trace minerals like iodine and zinc is quite common in certain populations. Children have food preferences and they are quite fussy to take green leafy vegetables and fruits thus compromising their intake of micronutrients from dietary sources. The full genetic potential of the child for physical growth and mental development may be compromised due to subclinical deficiencies of micronutrients which are commonly referred to as "hidden hunger". Micronutrients are required for the integrity and optimal functioning of immune system. Children with subclinical deficiency of micronutrients are more vulnerable to develop frequent and more severe common day-to-day infections thus triggering a vicious cycle of undernutrition and recurrent infections. A number of micronutrients are required for optimal physical growth and neuromotor development. Isolated deficiencies of micronutrients are rare in clinical practice and usually deficiencies of multiple micronutrients co-exist. The first 3 years of life are most crucial and vulnerable to the hazards of undernutrition. All efforts should be made so that preschool children are given a balanced and nutritious home-based diet. However, it has been shown that it is not possible to meet 100% requirements of recommended dietary allowances (RDA's) of micronutrients from dietary sources alone and most preschool children need administration of nutritional supplements to optimize their genetic potential for physical growth and mental development.

Ethnicity and alcohol-related fatalities : 1990 to 1994

DOT National Transportation Integrated Search

2000-07-01

Author's abstract: This paper contains a preliminary analysis of just under 200,000 records of fatally injured road users drawn from the 1990 to 1994 Fatality Analysis Reporting System (FARS). The analysis of ethnic factors in fatal crashes was made ...

2007 Washington State collision data summary

DOT National Transportation Integrated Search

2008-10-13

In 2007, Washingtons traffic fatality rate decreased to 1.00 per 100 million vehicle miles traveled (VMT), the lowest fatality rate in state history. : Washington State is 27% below the 2007 U.S. fatality rate of 1.37 fatalities per 100 VMT. : Bet...

2009 Washington State collision data summary

DOT National Transportation Integrated Search

2010-07-02

In 2009, Washingtons traffic fatality rate decreased to 0.87 per 100 million vehicle miles traveled (VMT), the lowest fatality rate in state history. : Washington State is 33% below the 2009 U.S. preliminary fatality rate of 1.16 fatalities per 10...

2008 Washington State collision data summary

DOT National Transportation Integrated Search

2009-07-28

In 2008, Washingtons traffic fatality rate decreased to 0.94 per 100 million vehicle miles traveled (VMT), the lowest fatality rate in state history. : Washington State is 35% below the 2008 U.S. fatality rate of 1.27 fatalities per 100 VMT. : Bet...

Crash Fatality Rates After Recreational Marijuana Legalization in Washington and Colorado.

PubMed

Aydelotte, Jayson D; Brown, Lawrence H; Luftman, Kevin M; Mardock, Alexandra L; Teixeira, Pedro G R; Coopwood, Ben; Brown, Carlos V R

2017-08-01

To evaluate motor vehicle crash fatality rates in the first 2 states with recreational marijuana legalization and compare them with motor vehicle crash fatality rates in similar states without recreational marijuana legalization. We used the US Fatality Analysis Reporting System to determine the annual numbers of motor vehicle crash fatalities between 2009 and 2015 in Washington, Colorado, and 8 control states. We compared year-over-year changes in motor vehicle crash fatality rates (per billion vehicle miles traveled) before and after recreational marijuana legalization with a difference-in-differences approach that controlled for underlying time trends and state-specific population, economic, and traffic characteristics. Pre-recreational marijuana legalization annual changes in motor vehicle crash fatality rates for Washington and Colorado were similar to those for the control states. Post-recreational marijuana legalization changes in motor vehicle crash fatality rates for Washington and Colorado also did not significantly differ from those for the control states (adjusted difference-in-differences coefficient = +0.2 fatalities/billion vehicle miles traveled; 95% confidence interval = -0.4, +0.9). Three years after recreational marijuana legalization, changes in motor vehicle crash fatality rates for Washington and Colorado were not statistically different from those in similar states without recreational marijuana legalization. Future studies over a longer time remain warranted.

Delayed Language Development Due to Infantile Thiamine Deficiency

ERIC Educational Resources Information Center

Fattal-Valevski, Aviva; Azouri-Fattal, Iris; Greenstein, Yoram J.; Guindy, Michal; Blau, Ayala; Zelnik, Nathanel

2009-01-01

The aim of this study was to investigate the language development of 20 children who had been exposed to thiamine (vitamin B[subscript 1]) deficiency in infancy due to feeding with soy-based formula that was accidentally deficient of thiamine. In this case-control study, 20 children (12 males, eight females; mean age 31.8 mo [SD 4.1], range 24-39…

Skin Lesions Associated with Nutritional Management of Maple Syrup Urine Disease

PubMed Central

Uaariyapanichkul, Jaraspong; Saengpanit, Puthita; Damrongphol, Ponghatai; Suphapeetiporn, Kanya

2017-01-01

Introduction Maple syrup urine disease (MSUD) is an inborn error of branched chain amino acids (BCAAs) metabolism. We report an infant with MSUD who developed 2 episodes of cutaneous lesions as a result of isoleucine deficiency and zinc deficiency, respectively. Case Presentation A 12-day-old male infant was presented with poor milk intake and lethargy. The diagnosis of MSUD was made based on clinical and biochemical data. Management and Outcome Specific dietary restriction of BCAAs was given. Subsequently, natural protein was stopped as the patient developed hospital-acquired infections which resulted in an elevation of BCAAs. Acrodermatitis dysmetabolica developed and was confirmed to be from isoleucine deficiency. At the age of 6 months, the patient developed severe lethargy and was on natural protein exclusion for an extended period. Despite enteral supplementation of zinc sulfate, cutaneous manifestations due to zinc deficiency occurred. Discussion Skin lesions in MSUD patients could arise from multiple causes. Nutritional deficiency including isoleucine and zinc deficiencies can occur and could complicate the treatment course as a result of malabsorption, even while on enteral supplementation. Parenteral nutrition should be considered and initiated accordingly. Clinical status, as well as BCAA levels, should be closely monitored in MSUD patients. PMID:29209542

Developmental vitamin D deficiency alters MK-801-induced behaviours in adult offspring.

PubMed

Kesby, James P; O'Loan, Jonathan C; Alexander, Suzanne; Deng, Chao; Huang, Xu-Feng; McGrath, John J; Eyles, Darryl W; Burne, Thomas H J

2012-04-01

Developmental vitamin D (DVD) deficiency is a candidate risk factor for developing schizophrenia in humans. In rodents DVD deficiency induces subtle changes in the way the brain develops. This early developmental insult leads to select behavioural changes in the adult, such as an enhanced response to amphetamine-induced locomotion in female DVD-deficient rats but not in male DVD-deficient rats and an enhanced locomotor response to the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in male DVD-deficient rats. However, the response to MK-801-induced locomotion in female DVD-deficient rats is unknown. Therefore, the aim of the current study was to further examine this behavioural finding in male and female rats and assess NMDA receptor density. DVD-deficient Sprague Dawley rats were assessed for locomotion, ataxia, acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR to multiple doses of MK-801. The NMDA receptor density in relevant brain regions was assessed in a drug-naive cohort. DVD deficiency increased locomotion in response to MK-801 in both sexes. DVD-deficient rats also showed an enhanced ASR compared with control rats, but PPI was normal. Moreover, DVD deficiency decreased NMDA receptor density in the caudate putamen of both sexes. These results suggest that a transient prenatal vitamin D deficiency has a long-lasting effect on NMDA-mediated signalling in the rodent brain and may be a plausible candidate risk factor for schizophrenia and other neuropsychiatric disorders.

Fatal crashes involving large numbers of vehicles and weather.

PubMed

Wang, Ying; Liang, Liming; Evans, Leonard

2017-12-01

Adverse weather has been recognized as a significant threat to traffic safety. However, relationships between fatal crashes involving large numbers of vehicles and weather are rarely studied according to the low occurrence of crashes involving large numbers of vehicles. By using all 1,513,792 fatal crashes in the Fatality Analysis Reporting System (FARS) data, 1975-2014, we successfully described these relationships. We found: (a) fatal crashes involving more than 35 vehicles are most likely to occur in snow or fog; (b) fatal crashes in rain are three times as likely to involve 10 or more vehicles as fatal crashes in good weather; (c) fatal crashes in snow [or fog] are 24 times [35 times] as likely to involve 10 or more vehicles as fatal crashes in good weather. If the example had used 20 vehicles, the risk ratios would be 6 for rain, 158 for snow, and 171 for fog. To reduce the risk of involvement in fatal crashes with large numbers of vehicles, drivers should slow down more than they currently do under adverse weather conditions. Driver deaths per fatal crash increase slowly with increasing numbers of involved vehicles when it is snowing or raining, but more steeply when clear or foggy. We conclude that in order to reduce risk of involvement in crashes involving large numbers of vehicles, drivers must reduce speed in fog, and in snow or rain, reduce speed by even more than they already do. Copyright © 2017 National Safety Council and Elsevier Ltd. All rights reserved.

[Leigh syndrome and leukodystrophy due to partial succinate dehydrogenase deficiency: regression with riboflavin].

PubMed

Pinard, J M; Marsac, C; Barkaoui, E; Desguerre, I; Birch-Machin, M; Reinert, P; Ponsot, G

1999-04-01

Succinate dehydrogenase (SDH) deficiency is rare. Clinical manifestations can appear in infancy with a marked impairment of psychomotor development with pyramidal signs and extrapyramidal rigidity. A 10-month-old boy developed severe neurological features, evoking a Leigh syndrome; magnetic resonance imaging showed features of leukodystrophy. A deficiency in the complex II respiratory chain (succinate dehydrogenase [SDH]) was shown. The course was remarkable by the regression of neurological impairment under treatment by riboflavin. The delay of psychomotor development, mainly involving language, was moderate at the age of 5 years. The relatively good prognosis of this patient, despite severe initial neurological impairment, may be due to the partial enzyme deficiency and/or riboflavin administration.

Analysis of fatal crashes due to signal and stop sign violations

DOT National Transportation Integrated Search

2004-09-01

The 1999 and 2000 Fatality Analysis Reporting System databases were analyzed to gain a better understanding of fatal crashes involving light vehicles that violated traffic signals or stop signs. A total of 9,951 vehicles were involved in fatal crashe...

Vitamin and mineral deficiencies in the developed world and their effect on the eye and vision.

PubMed

Whatham, Andrew; Bartlett, Hannah; Eperjesi, Frank; Blumenthal, Caron; Allen, Jane; Suttle, Catherine; Gaskin, Kevin

2008-01-01

Vitamin and mineral deficiencies are common in developing countries, but also occur in developed countries. We review micronutrient deficiencies for the major vitamins A, cobalamin (B(12)), biotin (vitamin H), vitamins C and E, as well as the minerals iron, and zinc, in the developed world, in terms of their relationship to systemic health and any resulting ocular disease and/or visual dysfunction. A knowledge of these effects is important as individuals with consequent poor ocular health and reduced visual function may present for ophthalmic care.

Impact of texting laws on motor vehicular fatalities in the United States.

PubMed

Ferdinand, Alva O; Menachemi, Nir; Sen, Bisakha; Blackburn, Justin L; Morrisey, Michael; Nelson, Leonard

2014-08-01

Using a panel study design, we examined the effects of different types of texting bans on motor vehicular fatalities. We used the Fatality Analysis Reporting System and a difference-in-differences approach to examine the incidence of fatal crashes in 2000 through 2010 in 48 US states with and without texting bans. Age cohorts were constructed to examine the impact of these bans on age-specific traffic fatalities. Primarily enforced laws banning all drivers from texting were significantly associated with a 3% reduction in traffic fatalities in all age groups, and those banning only young drivers from texting had the greatest impact on reducing deaths among those aged 15 to 21 years. Secondarily enforced restrictions were not associated with traffic fatality reductions in any of our analyses.

Impact of Texting Laws on Motor Vehicular Fatalities in the United States

PubMed Central

Ferdinand, Alva O.; Blackburn, Justin L.; Morrisey, Michael; Nelson, Leonard

2014-01-01

Using a panel study design, we examined the effects of different types of texting bans on motor vehicular fatalities. We used the Fatality Analysis Reporting System and a difference-in-differences approach to examine the incidence of fatal crashes in 2000 through 2010 in 48 US states with and without texting bans. Age cohorts were constructed to examine the impact of these bans on age-specific traffic fatalities. Primarily enforced laws banning all drivers from texting were significantly associated with a 3% reduction in traffic fatalities in all age groups, and those banning only young drivers from texting had the greatest impact on reducing deaths among those aged 15 to 21 years. Secondarily enforced restrictions were not associated with traffic fatality reductions in any of our analyses. PMID:24922151

Fatal work injuries involving natural disasters, 1992-2006.

PubMed

Fayard, Gregory M

2009-12-01

Although a goal of disaster preparedness is to protect vulnerable populations from hazards, little research has explored the types of risks that workers face in their encounters with natural disasters. This study examines how workers are fatally injured in severe natural events. A classification structure was created that identified the physical component of the disaster that led to the death and the pursuit of the worker as it relates to the disaster. Data on natural disasters from the Census of Fatal Occupational Injuries for the years 1992 through 2006 were analyzed. A total of 307 natural disaster deaths to workers were identified in 1992-2006. Most fatal occupational injuries were related to wildfires (80 fatalities), hurricanes (72 fatalities), and floods (62 fatalities). Compared with fatal occupational injuries in general, natural disaster fatalities involved more workers who were white and more workers who were working for the government. Most wildfire fatalities stemmed directly from exposure to fire and gases and occurred to those engaged in firefighting, whereas hurricane fatalities tended to occur more independently of disaster-produced hazards and to workers engaged in cleanup and reconstruction. Those deaths related to the 2005 hurricanes occurred a median of 36.5 days after landfall of the associated storm. Nearly half of the flood deaths occurred to passengers in motor vehicles. Other disasters included tornadoes (33 fatalities), landslides (17), avalanches (16), ice storms (14), and blizzards (9). Despite an increasing social emphasis on disaster preparation and response, there has been little increase in expert knowledge about how people actually perish in these large-scale events. Using a 2-way classification structure, this study identifies areas of emphasis in preventing occupational deaths from various natural disasters.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

PubMed

See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

2016-09-01

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

Estimation of fatality and injury risk by means of in-depth fatal accident investigation data.

PubMed

Yannis, George; Papadimitriou, Eleonora; Dupont, Emmanuelle; Martensen, Heike

2010-10-01

In this article the factors affecting fatality and injury risk of road users involved in fatal accidents are analyzed by means of in-depth accident investigation data, with emphasis on parameters not extensively explored in previous research. A fatal accident investigation (FAI) database is used, which includes intermediate-level in-depth data for a harmonized representative sample of 1300 fatal accidents in 7 European countries. The FAI database offers improved potential for analysis, because it includes information on a number of variables that are seldom available, complete, or accurately recorded in road accident databases. However, the fact that only fatal accidents are examined requires for methodological adjustments, namely, the correction for two types of effects on a road user's baseline risk: "accident size" effects, and "relative vulnerability" effects. Fatality and injury risk can be then modeled through multilevel logistic regression models, which account for the hierarchical dependences of the road accident process. The results show that the baseline fatality risk of road users involved in fatal accidents decreases with accident size and increases with the vulnerability of the road user. On the contrary, accident size increases nonfatal injury risk of road users involved in fatal accidents. Other significant effects on fatality and injury risk in fatal accidents include road user age, vehicle type, speed limit, the chain of accident events, vehicle maneuver, and safety equipment. In particular, the presence and use of safety equipment such as seat belt, antilock braking system (ABS), and electronic stability program (ESP) are protection factors for car occupants, especially for those seated at the front seats. Although ABS and ESP systems are typically associated with positive effects on accident occurrence, the results of this research revealed significant related effects on accident severity as well. Moreover, accident consequences are more severe when the most harmful event of the accident occurs later within the accident chain.

Fatally injured pedestrians and bicyclists in the United States with high blood alcohol concentrations.

PubMed

Eichelberger, Angela H; McCartt, Anne T; Cicchino, Jessica B

2018-06-01

Little research has focused on the problem of alcohol impairment among pedestrians and bicyclists in the United States. The aim of the current study was to investigate the prevalence, trends, and characteristics of alcohol-impaired fatally injured pedestrians and bicyclists. Data from the Fatality Analysis Reporting System (FARS) were analyzed for fatally injured passenger vehicle drivers, pedestrians, and bicyclists 16 and older during 1982-2014. Logistic regression models examined whether personal, roadway, and crash characteristics were associated with high blood alcohol concentrations (BACs) among fatally injured pedestrians and bicyclists. From 1982 to 2014, the percentage of fatally injured pedestrians with high BACs (≥0.08g/dL) declined from 45% to 35%, and the percentage of fatally injured bicyclists with high BACs declined from 28% to 21%. By comparison, the percentage of fatally injured passenger vehicle drivers with high BACs declined from 51% in 1982 to 32% in 2014. The largest reductions in alcohol impairment among fatally injured pedestrians and bicyclists were found among ages 16-20. During 2010-2014, fatally injured pedestrians and bicyclists ages 40-49 had the highest odds of having a high BAC, compared with other age groups. A substantial proportion of fatally injured pedestrians and bicyclists have high BACs, and this proportion has declined less dramatically than for fatally injured passenger vehicle drivers during the past three decades. Most countermeasures used to address alcohol-impaired driving may have only limited effectiveness in reducing fatalities among alcohol-impaired pedestrians and bicyclists. Efforts should increase public awareness of the risk of walking or bicycling when impaired. Results suggest the primary target audience for educational campaigns directed at pedestrians and bicyclists is middle-age males. Further research should evaluate the effectiveness of potential countermeasures, such as lowering speeds or improving lighting in urban areas. Copyright © 2018 National Safety Council and Elsevier Ltd. All rights reserved.

Dissociative phenomena in congenital monocular elevation deficiency.

PubMed

Olson, R J; Scott, W E

1998-04-01

Monocular elevation deficiency is characterized by unilateral limitation of elevation in both adduction and abduction and is usually present at birth. Dissociative phenomena such as dissociated vertical deviation are well recognized in association with conditions such as congenital esotropia but much less so in association with conditions such as congenital monocular elevation deficiency. All 129 patients given the diagnosis of monocular elevation deficiency or double elevator palsy in the Pediatric Ophthalmology and Strabismus Clinic at the University of Iowa Hospitals and Clinics between 1971 and 1995 were reviewed. After those with history of trauma, myasthenia gravis, thyroid eye disease, orbital lesions, Brown syndrome, or monocular elevation deficiency with acquired onset were excluded, 31 patients with congenital monocular elevation deficiency remained for retrospective study. First diagnosed at median age 2.6 years (although all were noted by parents at less than 6 months of age) with mean follow-up of 5.0 years (up to 15.5 years), 9 of 31 (29%) developed dissociated vertical deviation in the eye with monocular elevation deficiency, all of whom had undergone strabismus surgery 0 to 9.7 years previously (mean 3.5 years). Those who developed dissociated vertical deviation were generally younger, were followed up longer, and had more accompanying horizontal strabismus than did those who did not develop dissociated vertical deviation. The results did not reach significance. The current study demonstrates that dissociated vertical deviation occurs in association with monocular elevation deficiency.

Moving beyond teen crash fatality statistics : the go-team study.

DOT National Transportation Integrated Search

2013-04-08

Despite a trend of decreasing teen fatalities due to motor vehicle crashes over the past decade, they remain the leading cause : of adolescent fatalities in Iowa. The purpose of this study was to create detailed case studies of each fatal motor vehic...

The unsafe driving acts of motorists in the vicinity of large trucks

DOT National Transportation Integrated Search

1999-11-01

In 1996 large trucks composed 8% of all vehicles involved in fatal crashes; however, truck-involved crashes resulted in 12% of the total fatalities. Occupants of large trucks compose only 14% of the fatalities resulting from fatal truck crashes; 86% ...

2006 Washington State collision data summary

DOT National Transportation Integrated Search

2007-06-11

Between 1980 and 2006, the U.S. fatality rate has declined by 58% (from 3.35 to 1.42 fatalities per 100 million VMT). By comparison, during the same period, Washington states overall fatality rate has declined by 67% (from 3.43 to 1.12 fatalities ...

Nonoccupational logging fatalities--Vermont, 1997-2007.

PubMed

2008-03-14

Professional logging is one of the most hazardous occupations in the United States, and the factors contributing to injuries and fatalities associated with this occupation are well documented. However, little has been reported about logging fatalities in the nonoccupational setting. To better characterize nonoccupational logging fatalities, the Vermont Department of Health analyzed medical examiner data from Vermont for the period 1997-2007. This report describes four cases and summarizes data on all nonoccupational logging fatalities. The findings indicated that tree felling accounted for 15 (83%) of the 18 nonoccupational logging fatalities during the 11-year period and that 14 (78%) of the fatalities were attributed to injuries resulting from being struck by a falling tree or limb. Contributing factors in these incidents included absence of personal protective equipment (PPE), misjudgment of the path of falling trees, and being alone. Measures to reduce nonoccupational logging fatalities should focus on promoting safe tree-felling practices and increasing helmet use among nonprofessional woodcutters. Ideally, however, nonprofessionals should not participate in tree felling.

Factors associated with single-vehicle and multi-vehicle road traffic collision injuries in Ireland.

PubMed

Donnelly-Swift, Erica; Kelly, Alan

2016-12-01

Generalised linear regression models were used to identify factors associated with fatal/serious road traffic collision injuries for single- and multi-vehicle collisions. Single-vehicle collisions and multi-vehicle collisions occurring during the hours of darkness or on a wet road surface had reduced likelihood of a fatal/serious injury. Single-vehicle 'driver with passengers' collisions occurring at junctions or on a hill/gradient were less likely to result in a fatal/serious injury. Multi-vehicle rear-end/angle collisions had reduced likelihood of a fatal/serious injury. Single-vehicle 'driver only' collisions and multi-vehicle collisions occurring on a public/bank holiday or on a hill/gradient were more likely to result in a fatal/serious injury. Single-vehicle collisions involving male drivers had increased likelihood of a fatal/serious injury and single-vehicle 'driver with passengers' collisions involving drivers under the age of 25 years also had increased likelihood of a fatal/serious injury. Findings can enlighten decision-makers to circumstances leading to fatal/serious injuries.

Global earthquake fatalities and population

USGS Publications Warehouse

Holzer, Thomas L.; Savage, James C.

2013-01-01

Modern global earthquake fatalities can be separated into two components: (1) fatalities from an approximately constant annual background rate that is independent of world population growth and (2) fatalities caused by earthquakes with large human death tolls, the frequency of which is dependent on world population. Earthquakes with death tolls greater than 100,000 (and 50,000) have increased with world population and obey a nonstationary Poisson distribution with rate proportional to population. We predict that the number of earthquakes with death tolls greater than 100,000 (50,000) will increase in the 21st century to 8.7±3.3 (20.5±4.3) from 4 (7) observed in the 20th century if world population reaches 10.1 billion in 2100. Combining fatalities caused by the background rate with fatalities caused by catastrophic earthquakes (>100,000 fatalities) indicates global fatalities in the 21st century will be 2.57±0.64 million if the average post-1900 death toll for catastrophic earthquakes (193,000) is assumed.

BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation.

PubMed

Iwamoto, Shotaro; Azuma, Eiichi; Hori, Hiroki; Hirayama, Masahiro; Kobayashi, Michihiro; Komada, Yoshihiro; Nishimori, Hisashi; Miyahara, Masazumi

2002-06-01

The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a frequent and, seldom life-threatening complication after bone marrow transplantation (BMT). The authors report a male with melodysplastic syndrome, who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated BMT. His urine contained epithelial cells with intranuclear inclusion bodies suggestive of BKV infection and was positive for BKV in polymerase chain reaction. He did not respond to any treatment for HC. In addition, he developed BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive disease on day 42. This is the first case in which BKV may be associated with fatal progressive renal failure.

Objectifying when to halt a boxing match: a video analysis of fatalities.

PubMed

Miele, Vincent J; Bailes, Julian E

2007-02-01

Although numerous prestigious medical organizations have called for its abolishment, participation in the sport of boxing has reached an all-time high among both men and women, and its elimination is unlikely in the near future. Physicians should strive to increase boxing safety by improving the rules of competition, which have evolved minimally over the past two centuries. Currently, subjective criteria are used to determine whether or not a contest should be halted. Developing a standardized, objective method of determining when a contest should be halted would be a significant paradigm shift and could increase the safety of the sport's participants. This study analyzed the number and types of punches landed in a typical professional match, in bouts considered to be competitive and in those that ended in fatalities, to determine whether or not this would be a practical method of differentiating between these groups. Three groups of professional boxing matches were defined at the beginning of the study: 1) a "fatal" group, consisting of bouts that resulted in the death of a participant; 2) a "classic" group that represented competitive matches; and 3) a "control" group of 4000 professional boxing matches representing the average bout. A computer program known as Punchstat (Compubox, Inc., Manorville, NY) was used in the objective analysis of these matches via videotape playback. Several statistically significant differences were discovered between matches that resulted in fatalities and the control group. These include the number of punches landed per round, the number of power punches landed per round, and the number of power punches thrown per round by losing boxers. However, when the fatal bouts were compared with the most competitive bouts, these differences were no longer evident. Based on the data analyzed between the control and fatal-bout groups, a computerized method of counting landed blows at ringside could provide sufficient data to stop matches that might result in fatalities. However, such a process would become less effective as matches become more competitive, and implementing such a change would significantly decrease the competitive nature of the sport. Therefore, other methods of quantifying acceleration-deceleration brain injuries are necessary to improve the safety of boxing.

Estimating cost ratio distribution between fatal and non-fatal road accidents in Malaysia

NASA Astrophysics Data System (ADS)

Hamdan, Nurhidayah; Daud, Noorizam

2014-07-01

Road traffic crashes are a global major problem, and should be treated as a shared responsibility. In Malaysia, road accident tragedies kill 6,917 people and injure or disable 17,522 people in year 2012, and government spent about RM9.3 billion in 2009 which cost the nation approximately 1 to 2 percent loss of gross domestic product (GDP) reported annually. The current cost ratio for fatal and non-fatal accident used by Ministry of Works Malaysia simply based on arbitrary value of 6:4 or equivalent 1.5:1 depends on the fact that there are six factors involved in the calculation accident cost for fatal accident while four factors for non-fatal accident. The simple indication used by the authority to calculate the cost ratio is doubted since there is lack of mathematical and conceptual evidence to explain how this ratio is determined. The main aim of this study is to determine the new accident cost ratio for fatal and non-fatal accident in Malaysia based on quantitative statistical approach. The cost ratio distributions will be estimated based on Weibull distribution. Due to the unavailability of official accident cost data, insurance claim data both for fatal and non-fatal accident have been used as proxy information for the actual accident cost. There are two types of parameter estimates used in this study, which are maximum likelihood (MLE) and robust estimation. The findings of this study reveal that accident cost ratio for fatal and non-fatal claim when using MLE is 1.33, while, for robust estimates, the cost ratio is slightly higher which is 1.51. This study will help the authority to determine a more accurate cost ratio between fatal and non-fatal accident as compared to the official ratio set by the government, since cost ratio is an important element to be used as a weightage in modeling road accident related data. Therefore, this study provides some guidance tips to revise the insurance claim set by the Malaysia road authority, hence the appropriate method that suitable to implement in Malaysia can be analyzed.

Nighttime driving and fatal crash involvement of teenagers.

PubMed

Williams, A F

1985-02-01

Data from the 1977 National Personal Transportation Survey and from the Fatal Accident Reporting System were used to compute mileage-based fatal crash involvement rates of drivers, by age, sex, and time of day. Teenagers drive less than older drivers but do more of their driving at night. They have much higher numbers of drivers in fatal crashes based on miles driven than do older drivers; their nighttime rates are particularly high. Sixteen year olds, especially males, have by far the highest fatal crash rates per mile, both nighttime and daytime. More widespread adoption of driving curfew laws would very likely produce substantial reductions in fatalities involving 16 yr old drivers.

The effect of the 1997 Texas motorcycle helmet law on motorcycle crash fatalities.

PubMed

Bavon, Al; Standerfer, Christina

2010-01-01

This study seeks to determine the effect of the Texas motorcycle helmet law on fatalities since the repeal of the universal helmet law in 1997. Texas monthly motorcycle accident data between 1994 and 2004 were obtained from the National Highway Transportation Safety Administration's Fatality Analysis Reporting System (FARS) and supplemented with motorcycle registration data from the Texas Department of Transportation. An ARIMA model was used to estimate the impact of the law. A sharp increase in fatality rates occurred immediately following the implementation of the law in September 1997. Deaths increased by 30%, fatality rates per motorcycle registrations increased by 15.2%, and fatality rates per vehicle miles traveled increased by 25% after repeal. Helmet use decreased from 77% in 1996 to 63% in 1997 and 36% in 1998 and thereafter. The parameter estimates of the ARIMA model (0,0,0) (0,1,1) show that the change in the law led to statistically significant increases of 2.3 fatalities and 1.18 fatality rate per 100 billion vehicle miles traveled. The repeal of the universal helmet law in Texas in 1997 has had a significant adverse effect on motorcyclist fatalities in Texas.

Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke: EPIC-CVD case-cohort study.

PubMed

Ricci, Cristian; Wood, Angela; Muller, David; Gunter, Marc J; Agudo, Antonio; Boeing, Heiner; van der Schouw, Yvonne T; Warnakula, Samantha; Saieva, Calogero; Spijkerman, Annemieke; Sluijs, Ivonne; Tjønneland, Anne; Kyrø, Cecilie; Weiderpass, Elisabete; Kühn, Tilman; Kaaks, Rudolf; Sánchez, Maria-Jose; Panico, Salvatore; Agnoli, Claudia; Palli, Domenico; Tumino, Rosario; Engström, Gunnar; Melander, Olle; Bonnet, Fabrice; Boer, Jolanda M A; Key, Timothy J; Travis, Ruth C; Overvad, Kim; Verschuren, W M Monique; Quirós, J Ramón; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Peppa, Eleni; Iribas, Conchi Moreno; Gavrila, Diana; Forslund, Ann-Sofie; Jansson, Jan-Håkan; Matullo, Giuseppe; Arriola, Larraitz; Freisling, Heinz; Lassale, Camille; Tzoulaki, Ioanna; Sharp, Stephen J; Forouhi, Nita G; Langenberg, Claudia; Saracci, Rodolfo; Sweeting, Michael; Brennan, Paul; Butterworth, Adam S; Riboli, Elio; Wareham, Nick J; Danesh, John; Ferrari, Pietro

2018-05-29

To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Multicentre case-cohort study. A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Comparison of teen driver fatality rates by vehicle type in the United States.

PubMed

Trowbridge, Matthew J; McKay, Mary Pat; Maio, Ronald F

2007-10-01

To compare national fatality rates for teen drivers by vehicle type. Fatality rates were calculated for 16- to 19-year-old drivers by vehicle type using data from the Fatal Analysis Reporting System (1999-2003) and estimates of miles driven from the National Household Transportation Survey (2001). Relative fatality risks for teen drivers of sports utility vehicles (SUVs) and pickups were calculated using passenger cars as a reference. Per vehicle mile driven, the fatality risk for both male and female teens driving SUVs was decreased relative to passenger car drivers (male teens: relative risk [RR], 0.33 [95% confidence interval [CI] = 0.29 to 0.37]; female teens: RR, 0.45 [95% CI = 0.34 to 0.59]). Fatality rates for male teens driving pickups were also lower per mile driven compared with male passenger car drivers (RR, 0.55 [95% CI = 0.51 to 0.60]). Fatality rates for female teens driving pickups and passenger cars were not statistically different but appear potentially higher for pickups (RR, 1.19 [95% CI = 0.98 to 1.44]). Both SUVs and pickups demonstrated significantly higher rates of fatal rollovers than passenger cars. Female adolescent drivers of SUVs and pickups were at particularly high risk for fatal rollovers per vehicle mile driven compared with passenger cars (SUV: RR, 1.88 [95% CI = 1.19 to 2.96]; pickup: RR, 3.42 [95% CI = 2.29 to 5.10]). Fatality rates for teen drivers vary significantly by vehicle type. From 1999 to 2003 in the United States, fatal rollovers were significantly more likely per mile driven for teen drivers of both SUVs and pickups compared with passenger cars. However, overall fatality rates (i.e., all crash types) for teen drivers of SUVs and male drivers of pickups were lower per mile driven than for teen drivers of passenger cars. The results of this ecological analysis cannot predict the individual-level fatality risk for teens driving different vehicle types. However, the significant variability in fatality rates among SUVs, pickups, and passenger cars seen at a population level suggests that vehicle choice should be further explored as a potentially modifiable risk factor in interventions to address teen driver safety.

Factors associated with fatal pedestrian crashes in Virginia's urban areas-1985-1987 : final report.

DOT National Transportation Integrated Search

1991-01-01

Between 1985 and 1987, a total of 400 pedestrians were fatally injured in Virginia; more than half of the pedestrian fatalities occurred in an urban area of the Commonwealth. Because little research had been conducted on urban pedestrian fatalities i...

Assessing farm tractor incidents and awareness levels of operators for tractor safety issues in the Hatay province of Turkey.

PubMed

Keskin, S Görücü; Keskin, M; Soysal, Y

2012-04-01

Studies and statistical data on safety issues related to farm tractors and machinery are very limited in developing countries, including Turkey. This study was carried out to investigate tractor-related incidents in the Hatay province, located in the mid-south of Turkey. A questionnaire was conducted with 107 tractor operators using face-to-face interviews. Data were evaluated according to the incident type, machinery involved, and mechanism of injury or fatality. A total of 101 incidents were reported by 77 of the 107 respondents. Most of the incidents were due to tractor rollovers (65.4%), 14.8% of the incidents were due to entanglement of body parts in moving machinery, and 12.9% involved crashing into other vehicles or obstacles. The leading cause of the incidents was personal mistakes (60.4%). Fatalities resulted from 25.7% of the incidents, while 45.5% of the incidents caused non-fatal injuries. Only 5.6% of the tractors had a ROPS-enclosed cab. The percentage of ROPS-equipped tractors was 19.6%, while 41.3% of the tractors had a shade cover and 33.6% had no protective structure. Only one of the respondents used a seatbelt, although 44.9% of them stated that seatbelts should be used. It was also found that only 13.5% of the operators had training in work safety, while 95.1% stated that incidents might be reduced if people were trained. Development of appropriate policies and training programs are needed for safer operation of agricultural machinery to reduce injuries and fatalities due to farm accidents.

Fatal acute pulmonary injury associated with everolimus.

PubMed

Depuydt, Pieter; Nollet, Joke; Benoit, Dominique; Praet, Marleen; Caes, Frank

2012-03-01

To report a case of fatal alveolar hemorrhage associated with the use of everolimus in a patient who underwent a solid organ transplant. In a 71-year-old cardiac transplant patient, cyclosporine was replaced with everolimus because of worsening renal function. Over the following weeks, the patient developed nonproductive cough and increasing dyspnea. His condition deteriorated to acute respiratory failure with hemoptysis, requiring hospital admission. Bilateral patchy alveolar infiltrates were apparent on chest X-ray and computed tomography. Cardiac failure was ruled out and empiric antimicrobial therapy was initiated. Additional extensive workup could not document opportunistic infection. Everolimus was discontinued and high-dose corticosteroid therapy was initiated. Despite this, the patient required invasive mechanical ventilation and died because of refractory massive hemoptysis. Autopsy revealed diffuse alveolar hemorrhage. Everolimus is a mammalian target of rapamycin inhibitor approved for use as an immunosuppressant and antineoplastic agent. Its main advantage over calcineurin inhibitors (tacrolimus and cyclosporine) is a distinct safety profile. Although it has become clear that everolimus induces pulmonary toxicity more frequently than initially thought, most published cases thus far represented mild and reversible disease, and none was fatal. Here, we report a case of pulmonary toxicity developing over weeks following the introduction of everolimus, in which a fatal outcome could not be prevented by drug withdrawal and corticosteroid treatment. The association of everolimus and this syndrome was probable according to the Naranjo probability scale. This case indicates that with the increasing use of everolimus, clinicians should be aware of the rare, but life-threatening manifestation of pulmonary toxicity.

CD22 x Siglec-G double-deficient mice have massively increased B1 cell numbers and develop systemic autoimmunity.

PubMed

Jellusova, Julia; Wellmann, Ute; Amann, Kerstin; Winkler, Thomas H; Nitschke, Lars

2010-04-01

CD22 and Siglec-G are inhibitory coreceptors for BCR-mediated signaling. Although CD22-deficient mice show increased calcium signaling in their conventional B2 cells and a quite normal B cell maturation, Siglec-G-deficient mice have increased calcium mobilization just in B1 cells and show a large expansion of the B1 cell population. Neither CD22-deficient, nor Siglec-G-deficient mice on a pure C57BL/6 or BALB/c background, respectively, develop autoimmunity. Using Siglec-G x CD22 double-deficient mice, we addressed whether Siglec-G and CD22 have redundant functions. Siglec-G x CD22 double-deficient mice show elevated calcium responses in both B1 cells and B2 cells, increased serum IgM levels and an enlarged population of B1 cells. The enlargement of B1 cell numbers is even higher than in Siglecg(-/-) mice. This expansion seems to happen at the expense of B2 cells, which are reduced in absolute cell numbers, but show an activated phenotype. Furthermore, Siglec-G x CD22 double-deficient mice show a diminished immune response to both thymus-dependent and thymus-independent type II Ags. In contrast, B cells from Siglec-G x CD22 double-deficient mice exhibit a hyperproliferative response to stimulation with several TLR ligands. Aged Siglec-G x CD22 double-deficient mice spontaneously develop anti-DNA and antinuclear autoantibodies. These resulted in a moderate form of immune complex glomerulonephritis. These results show that Siglec-G and CD22 have partly compensatory functions and together are crucial in maintaining the B cell tolerance.

Fetal and Neonatal Iron Deficiency Exacerbates Mild Thyroid Hormone Insufficiency Effects on Male Thyroid Hormone Levels and Brain Thyroid Hormone-Responsive Gene Expression

PubMed Central

Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.

2014-01-01

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression. PMID:24424046

Deficient maternal zinc intake-but not folate-is associated with lower fetal heart rate variability.

PubMed

Spann, Marisa N; Smerling, Jennifer; Gustafsson, Hanna; Foss, Sophie; Altemus, Margaret; Monk, Catherine

2015-03-01

Few studies of maternal prenatal diet and child development examine micronutrient status in relation to fetal assessment. Twenty-four-hour dietary recall of zinc and folate and 20min of fetal heart rate were collected from 3rd trimester pregnant adolescents. Deficient zinc was associated with less fetal heart rate variability. Deficient folate had no associations with HRV. Neither deficient zinc nor deficient folate was related to fetal heart rate. These findings, from naturalistic observation, are consistent with emerging data on prenatal zinc supplementation using a randomized control design. Taken together, the findings suggest that maternal prenatal zinc intake is an important and novel factor for understanding child ANS development. Copyright © 2015. Published by Elsevier Ireland Ltd.

Micronutrient deficiencies in early childhood can lower a country's GDP: The Myanmar example.

PubMed

Win, Aung Zaw

2016-01-01

Myanmar (Burma) is a developing country in South East Asia. While Myanmar is among the 20 countries where 80% of the world's malnourished children live, its military consumes the majority of the national budget. Children who are malnourished between conception and age two are at high risk for impaired physical and mental development, which adversely affects the country's productivity and growth. Myanmar is facing three major micronutrient deficiencies which are iodine, iron and vitamin A deficiencies. The three micronutrient deficiencies can cost about 2.4% of the country's GDP. Children are the future of Myanmar and persistent micronutrient deficiencies will hamper its economic growth and lower its GDP. Copyright © 2016 Elsevier Inc. All rights reserved.

Fire fighter fatalities 1998–2001: overview with an emphasis on structure related traumatic fatalities

PubMed Central

Hodous, T; Pizatella, T; Braddee, R; Castillo, D

2004-01-01

Objective: To review the causes of all fire fighter line-of-duty-deaths from 1998 through 2001, and present recommendations for preventing fatalities within the specific subgroup of structure related events. Methods: Fire fighter fatality data from the United States Fire Administration were reviewed and classified into three main categories of injury. Investigations conducted through the National Institute for Occupational Safety and Health (NIOSH) Fire Fighter Fatality Investigation and Prevention Program provided the basis for the recommendations presented in this paper. Results: During the time period from 1998–2001, there were 410 line-of-duty deaths among fire fighters in the United States, excluding the 343 fire fighters who died at the World Trade Center on 11 September 2001. The 410 fatalities included 191 medical (non-traumatic) deaths (47%), 75 motor vehicle related fatalities (18%), and 144 other traumatic fatalities (35%). The latter group included 68 fatalities that were associated with structures which commonly involved structural collapse, rapid fire progression, and trapped fire fighters. Conclusions: Structural fires pose particular hazards to fire fighters. Additional efforts must be directed to more effectively use what we have learned through the NIOSH investigations and recommendations from published experts in the safety community, consensus standards, and national fire safety organizations to reduce fire fighter fatalities during structural fire fighting. PMID:15314049

The turning point in the number of traffic fatalities: two hypotheses about changes in underlying trends.

PubMed

Brüde, Ulf; Elvik, Rune

2015-01-01

The number of traffic fatalities reached a peak in many highly motorised countries around 1970. Some previous studies have suggested that the turning point in the number of traffic fatalities was inevitable and did not reflect a change in the underlying trends influencing the number of traffic fatalities. Other studies suggest that trends in traffic growth and fatality rate changed from before to after the turning point. This paper proposes two hypotheses about the turning point in the number of traffic fatalities. One hypothesis is that the long-term trends in traffic growth and fatality rate were the same before and after the turning point. The other hypothesis is that the long-term trends in traffic growth and fatality rate were different before and after the turning point was reached, in particular that the annual percentage decline in fatality rate became greater after the turning point than before. Such a change would suggest that road safety policy became more effective. Analysis of data for six countries (Denmark, Great Britain, Netherlands, Norway, Sweden, United States) lends stronger support to the latter hypothesis than to the former. The lesson for policy makers, in particular in countries where the number of traffic fatalities is still growing, is that they should not expect a turning point to be reached without policy interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Results from the Hawaii domestic violence fatality review, 2000-2009

PubMed Central

Pobutsky, Ann; Brown, Melissa; Nakao, Lisa; Reyes-Salvail, Florentina

2014-01-01

Abstract: Background: Patterns of domestic violence fatalities and agency responses in Hawaii have not been explicated. Methods: Retrospective reviews of events leading up to domestic violence related fatalities in Hawaii were assessed from 45 adjudicated cases that resulted in 62 fatalities for the ten year period from 2000-2009. Results: Almost one-half of the fatalities were homicide/suicide combinations. Females were disproportionately more likely to be fatal victims of domestic violence relative to their proportion in the population. Those aged 21-40 years and those over 80 years were more likely to be fatal victims of domestic violence, relative to their proportion in the population. Filipinas and ‘Other” ethnic groups are disproportionately more likely to be fatal victims of domestic violence while Native Hawaiians and Japanese are less likely to be fatal victims, relative to their proportions in the population. In more than two-thirds of the cases, the victim had made some attempt to leave the relationship prior to the fatality. Conclusions: In the majority of cases there was agency involvement in some form: either the victim alone or the perpetrator alone, or both. However, less than one-third (31.1%) of the cases over the past ten years had documentation of prior violence from medical reports, so this may be an area to further document and address domestic violence. PMID:24292165

Results from the Hawaii domestic violence fatality review, 2000-2009.

PubMed

Pobutsky, Ann; Brown, Melissa; Nakao, Lisa; Reyes-Salvail, Florentina

2014-07-01

Patterns of domestic violence fatalities and agency responses in Hawaii have not been explicated. Retrospective reviews of events leading up to domestic violence related fatalities in Hawaii were assessed from 45 adjudicated cases that resulted in 62 fatalities for the ten year period from 2000-2009. Almost one-half of the fatalities were homicide/suicide combinations. Females were disproportionately more likely to be fatal victims of domestic violence relative to their proportion in the population. Those aged 21-40 years and those over 80 years were more likely to be fatal victims of domestic violence, relative to their proportion in the population. Filipinas and 'Other" ethnic groups are disproportionately more likely to be fatal victims of domestic violence while Native Hawaiians and Japanese are less likely to be fatal victims, relative to their proportions in the population. In more than two-thirds of the cases, the victim had made some attempt to leave the relationship prior to the fatality. In the majority of cases there was agency involvement in some form: either the victim alone or the perpetrator alone, or both. However, less than one-third (31.1%) of the cases over the past ten years had documentation of prior violence from medical reports, so this may be an area to further document and address domestic violence. © 2014 KUMS, All rights reserved.

Vitamin A and micronutrient deficiencies post-bariatric surgery: aetiology, complications and management in a complex multiparous pregnancy.

PubMed

Mackie, Fiona L; Cooper, Nicola S; Whitticase, Louise J; Smith, Amanda; Martin, William L; Cooper, Sheldon C

2018-06-12

Adequate vitamin A is essential for healthy pregnancy, but high levels may be teratogenic. We present a patient who underwent bariatric surgery, prior to child bearing, and suffered maternal and foetal complications during eleven pregnancies, possibly associated with vitamin A deficiency, amongst multiple micronutrient deficiencies and risk factors including smoking and obesity. Maternal complications included visual disturbance, night blindness and recurrent infections. Recurrent foetal pulmonary hypoplasia and microphthalmia led to foetal and neonatal loss, not previously described in the medical literature. Current guidance on vitamin A deficiency in pregnancy is focused on developing countries where aetiology of vitamin A deficiency is different to that of women in developed countries. We describe nutritional management of the micronutritient deficiencies, focusing on vitamin A, during her last pregnancy. The need for specific antenatal nutritional guidance for pregnant women post-bariatric surgery is becoming more urgent as more mothers and offspring will be affected.

Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development.

PubMed

Beutler, Ernest; Duparc, Stephan

2007-10-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.

Work-related agricultural fatalities in Australia, 1982-1984.

PubMed

Erlich, S M; Driscoll, T R; Harrison, J E; Frommer, M S; Leigh, J

1993-06-01

Work-related agricultural fatalities were examined as part of a larger population-based study of all work-related fatalities in Australia in the period 1982-1984. A total of 257 farm-related fatalities were identified, of which 223 were deaths of persons in the employed civilian labor force (19.4 deaths per 100,000 persons per year) and 34 were deaths of children less than 15 years of age. The fatality incidence was higher among men, older age groups, and nonmanagers in general and in certain occupations in particular. Mobile mechanical equipment (particularly tractors) was the main fatal agent, roll-overs accounting for many of the fatalities. Better provision of information to agricultural workers, improvements in compliance to and enforcement of legislation, and changes in farming work practices are recommended to improve the safety of farms and farm work.

Type I interferon signals in macrophages and dendritic cells control dengue virus infection: implications for a new mouse model to test dengue vaccines.

PubMed

Züst, Roland; Toh, Ying-Xiu; Valdés, Iris; Cerny, Daniela; Heinrich, Julia; Hermida, Lisset; Marcos, Ernesto; Guillén, Gerardo; Kalinke, Ulrich; Shi, Pei-Yong; Fink, Katja

2014-07-01

Dengue virus (DENV) infects an estimated 400 million people every year, causing prolonged morbidity and sometimes mortality. Development of an effective vaccine has been hampered by the lack of appropriate small animal models; mice are naturally not susceptible to DENV and only become infected if highly immunocompromised. Mouse models lacking both type I and type II interferon (IFN) receptors (AG129 mice) or the type I IFN receptor (IFNAR(-/-) mice) are susceptible to infection with mouse-adapted DENV strains but are severely impaired in mounting functional immune responses to the virus and thus are of limited use for study. Here we used conditional deletion of the type I IFN receptor (IFNAR) on individual immune cell subtypes to generate a minimally manipulated mouse model that is susceptible to DENV while retaining global immune competence. Mice lacking IFNAR expression on CD11c(+) dendritic cells and LysM(+) macrophages succumbed completely to DENV infection, while mice deficient in the receptor on either CD11c(+) or LysM(+) cells were susceptible to infection but often resolved viremia and recovered fully from infection. Conditional IFNAR mice responded with a swift and strong CD8(+) T-cell response to viral infection, compared to a weak response in IFNAR(-/-) mice. Furthermore, mice lacking IFNAR on either CD11c(+) or LysM(+) cells were also sufficiently immunocompetent to raise a protective immune response to a candidate subunit vaccine against DENV-2. These data demonstrate that mice with conditional deficiencies in expression of the IFNAR represent improved models for the study of DENV immunology and screening of vaccine candidates. Dengue virus infects 400 million people every year worldwide, causing 100 million clinically apparent infections, which can be fatal if untreated. Despite many years of research, there are no effective vaccine and no antiviral treatment available for dengue. Development of vaccines has been hampered in particular by the lack of a suitable small animal model. Mouse models used to test dengue vaccine are deficient in interferon (IFN) type I signaling and severely immunocompromised and therefore likely not ideal for the testing of vaccines. In this study, we explored alternative models lacking the IFN receptor only on certain cell types. We show that mice lacking the IFN receptor on either CD11c- or LysM-expressing cells (conditional IFNAR mice) are susceptible to dengue virus infection. Importantly, we demonstrate that conditional IFN receptor knockout mice generate a better immune response to live virus and a candidate dengue vaccine compared to IFNAR mice and are resistant to subsequent challenge. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Does the probability of developing ocular trauma-related visual deficiency differ between genders?

PubMed

Blanco-Hernández, Dulce Milagros Razo; Valencia-Aguirre, Jessica Daniela; Lima-Gómez, Virgilio

2011-01-01

Ocular trauma affects males more often than females, but the impact of this condition regarding visual prognosis is unknown. We undertook this study to compare the probability of developing ocular trauma-related visual deficiency between genders, as estimated by the ocular trauma score (OTS). We designed an observational, retrospective, comparative, cross-sectional and open-label study. Female patients aged ≥6 years with ocular trauma were included and matched by age and ocular wall status with male patients at a 1:2 male/female ratio. Initial trauma features and the probability of developing visual deficiency (best corrected visual acuity <20/40) 6 months after the injury, as estimated by the OTS, were compared between genders. The proportion and 95% confidence intervals (95% CI) of visual deficiency 6 months after the injury were estimated. Ocular trauma features and the probability of developing visual deficiency were compared between genders (χ(2) and Fisher's exact test); p value <0.05 was considered significant. Included were 399 eyes (133 from females and 266 from males). Mean age of patients was 25.7 ± 14.6 years. Statistical differences existed in the proportion of zone III in closed globe trauma (p = 0.01) and types A (p = 0.04) and type B (p = 0.02) in open globe trauma. The distribution of the OTS categories was similar for both genders (category 5: p = 0.9); the probability of developing visual deficiency was 32.6% (95% CI = 24.6 to 40.5) in females and 33.2% (95% CI = 27.6 to 38.9) in males (p = 0.9). The probability of developing ocular trauma-related visual deficiency was similar for both genders. The same standard is required.

Insomnia Symptoms and Risk for Unintentional Fatal Injuries—The HUNT Study

PubMed Central

Laugsand, Lars Erik; Strand, Linn B.; Vatten, Lars J.; Janszky, Imre; Bjørngaard, Johan Håkon

2014-01-01

Study Objectives: To assess the association between insomnia symptoms and risk of fatal unintentional injuries. Design: Population-based prospective cohort study with a mean follow-up of 14 y, linking health survey data with information on insomnia symptoms to the National Cause of Death Registry. Setting: Nord-Trøndelag County, Norway. Participants: A total of 54,399 men and women 20-89 y of age who participated in the Nord-Trøndelag Health Study between 1995 and 1997. Interventions: N/A. Measurements and results: There were 277 unintentional fatal injuries, including 57 fatal motor vehicle injuries during follow-up. There was a dose-dependent association between the number of insomnia symptoms and risk of unintentional fatal injuries (P for trend 0.001) and fatal motor vehicle injuries (P for trend 0.023), respectively. The proportion of unintentional fatal injuries cases that could have been prevented in the absence of difficulties initiating sleep, difficulties maintaining sleep, and having a feeling of nonrestorative sleep were 8%, 9%, and 8%, respectively. The corresponding estimates for motor vehicle injuries were 34%, 11%, and 10%. Conclusion: Insomnia is a major contributor to both unintentional fatal injuries in general as well as fatal motor vehicle injuries. Increasing public health awareness about insomnia and identifying persons with insomnia may be important in preventing unintentional fatal injuries. Citation: Laugsand LE, Strand LB, Vatten LJ, Janszky I, Bjørngaard JH. Insomnia symptoms and risk for unintentional fatal injuries—the HUNT Study. SLEEP 2014;37(11):1777-1786. PMID:25364073

Deaths due to Intentional Explosions in Selected Governorates of Iraq from 2010 to 2013: Prospective Surveillance.

PubMed

Bilukha, Oleg O; Leidman, Eva Z; Sultan, Abdul-Salam Saleh; Jaffar Hussain, Syed

2015-12-01

The aim of this study was to describe the most recent trends and epidemiologic patterns of fatal injuries resulting from explosions in Iraq, one of the countries most affected by violence from explosive devices. Iraqi Ministry of Health (MoH) routine prospective injury surveillance collects information on all fatal injuries recorded by coroners from physical examinations, police reports, and family members in eight governorates of Iraq: Baghdad, Al-Anbar, Basrah, Erbil, Kerbala, Maysan, Ninevah, and Al-Sulaimaniya. This study analyzed explosive-related fatal injuries that occurred from January 1, 2010 through December 31, 2013. Analysis included 2,803 fatal injuries. The number of fatal injuries declined from 2010 through 2012, followed by an increase in 2013. One-thousand one-hundred and one explosion-related fatalities were documented in 2013, more than twice as many as in 2012 or in 2011. Most fatalities were among men aged 20-39 years. Of all causalities, 194 (6.9%) were among females and 302 (10.8%) were among children aged less than 18 years. The majority of fatalities were caused by improvised explosive devices (IEDs): car bombs (15.3%), suicide bombs (4.0%), and other IEDs (29.6%). The highest number of fatalities occurred in streets and roads. Of all deaths, 95.6% occurred in three governorates: Baghdad, Ninevah, and Al-Anbar. Explosives continue to result in a high number of fatal injuries in Iraq. Following a period of declining violence from explosives, in 2013, fatalities increased. Most explosion-related injuries resulted from IEDs; males aged 20-39 years were at greatest risk.

Effects of legislative reform to reduce drunken driving and alcohol-related traffic fatalities.

PubMed Central

Hingson, R W; Howland, J; Levenson, S

1988-01-01

From 1980 through 1985, considerable progress was made across the Nation in reducing drunken driving and fatal automobile crashes. More than 400 chapters of local citizen groups concerned with reducing drunken driving were formed. New media coverage, measured in number of stories, increased fiftyfold from 1980 to 1984. More than 500 legislative reforms were passed. All States now have adopted a legal drinking age of 21. Many also adopted criminal and administrative per se laws and instituted penalty increases for drunken driving. By 1985, the total number of fatal crashes declined to 39,168, a decrease of 6,116, or 16 percent, from the 1980 level of 45,284. Single-vehicle fatal crashes occurring at night, those most likely to involve alcohol, declined by 20 percent, with 3,674 fewer crashes in 1985 than in 1980. Among teenage drivers, declines in fatal crashes were steeper: Fatal crashes decreased 26 percent, and single-vehicle night fatal crashes were down 34 percent. After 1984, however, the number of new citizen groups established and the number of stories appearing in the media began to decline. In 1986, after decreasing for several years, the number of fatal crashes rose 5 percent, and single-vehicle night fatal crashes rose 7 percent, up 1,060 from 1985. Among teenage drivers, the increase in single-vehicle night fatal crashes was even higher, up 17 percent. In 1987, single-vehicle night fatal crashes declined slightly but still remained higher than in 1983, 1984, or 1985.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3141962

Specialty of prescribers associated with prescription opioid fatalities in Utah, 2002-2010.

PubMed

Porucznik, Christina A; Johnson, Erin M; Rolfs, Robert T; Sauer, Brian C

2014-01-01

Opioid adverse events are widespread, and deaths have been directly attributed to opioids prescribed by medical professionals. Little information exists on the amount of opioids various medical specialties prescribe and the opioid fatality rate that would be expected if prescription opioid-related deaths were independent of medical specialty. To compute the incidence of prescription opioid fatalities by medical specialty in Utah and to calculate the attributable risk (AR) of opioid fatality by medical specialty. Prevalence database study design linking the Utah Controlled Substance Database (CSD) for prescribing data with the Utah Medical Examiner data to identify prescription opioid fatalities. AR were calculated for each medical specialty and year. Opioid prescriptions are common with 23,302,892 recorded in the CSD for 2002-2010, 0.64% of which were associated with a fatality. We attached specialty to 90.2% of opioid prescriptions. Family medicine and internal medicine physicians wrote the largest proportion of prescriptions (24.1% and 10.8%) and were associated with the greatest number of prescription opioid fatalities. The number of active prescriptions at time of death decreased each year. The AR of fatality by provider specialty varied each year with some specialties, such as pain medicine and anesthesiology, consistently associated with more fatalities per 1,000 opioid prescriptions than internal medicine physicians the same year. Primary care providers were the most frequent prescribers and the most often associated with opioid fatalities and should be targeted for education about safe prescribing along with specialties that prescribe less frequently but are associated with a positive AR for opioid fatality. Wiley Periodicals, Inc.

An evaluation of the increase in traffic fatalities in Virginia in 1977.

DOT National Transportation Integrated Search

1978-01-01

Since the Arab oil embargo of 1973 the number of fatal traffic accidents and fatalities in Virginia has been relatively stable from year to year. However, in September 1977 fatalities began to occur at an alarming rate and by the end of 1977, the tot...

Effect of Dietary Iron on Fetal Growth in Pregnant Mice

PubMed Central

Hubbard, Andrea C; Bandyopadhyay, Sheila; Wojczyk, Boguslaw S; Spitalnik, Steven L; Hod, Eldad A; Prestia, Kevin A

2013-01-01

Iron deficiency is the most common nutritional disorder. Children and pregnant women are at highest risk for developing iron deficiency because of their increased iron requirements. Iron-deficiency anemia during pregnancy is associated with adverse effects on fetal development, including low birth weight, growth retardation, hypertension, intrauterine fetal death, neurologic impairment, and premature birth. We hypothesized that pregnant mice fed an iron-deficient diet would have a similar outcome regarding fetal growth to that of humans. To this end, we randomly assigned female C57BL/6 mice to consume 1 of 4 diets (high-iron–low-bioavailability, high-iron–high-bioavailability, iron-replete, and iron-deficient) for 4 wk before breeding, followed by euthanasia on day 17 to 18 of gestation. Compared with all other groups, dams fed the high-iron–high-bioavailability diet had significantly higher liver iron. Hct and Hgb levels in dams fed the iron-deficient diet were decreased by at least 2.5 g/dL as compared with those of all other groups. In addition, the percentage of viable pups among dams fed the iron-deficient diet was lower than that of all other groups. Finally, compared with all other groups, fetuses from dams fed the iron-deficient diet had lower fetal brain iron levels, shorter crown–rump lengths, and lower weights. In summary, mice fed an iron-deficient diet had similar hematologic values and fetal outcomes as those of iron-deficient humans, making this a useful model for studying iron-deficiency anemia during pregnancy. PMID:23582419

Phosphorus starvation induces post-transcriptional CHS gene silencing in Petunia corolla.

PubMed

Hosokawa, Munetaka; Yamauchi, Takayoshi; Takahama, Masayoshi; Goto, Mariko; Mikano, Sachiko; Yamaguchi, Yuki; Tanaka, Yoshiyuki; Ohno, Sho; Koeda, Sota; Doi, Motoaki; Yazawa, Susumu

2013-05-01

The corolla of Petunia 'Magic Samba' exhibits unstable anthocyanin expression depending on its phosphorus content. Phosphorus deficiency enhanced post-transcriptional gene silencing of chalcone synthase - A in the corolla. Petunia (Petunia hybrida) 'Magic Samba' has unstable red-white bicolored corollas that respond to nutrient deficiency. We grew this cultivar hydroponically using solutions that lacked one or several nutrients to identify the specific nutrient related to anthocyanin expression in corolla. The white area of the corolla widened under phosphorus (P)-deficient conditions. When the P content of the corolla grown under P-deficient conditions dropped to <2,000 ppm, completely white corollas continued to develop in >40 corollas until the plants died. Other elemental deficiencies had no clear effects on anthocyanin suppression in the corolla. After phosphate was resupplied to the P-deficient plants, anthocyanin was restored in the corollas. The expression of chalcone synthase-A (CHS-A) was suppressed in the white area that widened under P-suppressed conditions, whereas the expression of several other genes related to anthocyanin biosynthesis was enhanced more in the white area than in the red area. Reddish leaves and sepals developed under the P-deficient condition, which is a typical P-deficiency symptom. Two genes related to anthocyanin biosynthesis were enhanced in the reddish organs. Small interfering RNA analysis of CHS-A showed that the suppression resulted from post-transcriptional gene silencing (PTGS). Thus, it was hypothesized that the enhancement of anthocyanin biosynthetic gene expression due to P-deficiency triggered PTGS of CHS-A, which resulted in white corolla development.

Impaired embryonic development in glucose-6-phosphate dehydrogenase-deficient Caenorhabditis elegans due to abnormal redox homeostasis induced activation of calcium-independent phospholipase and alteration of glycerophospholipid metabolism.

PubMed

Chen, Tzu-Ling; Yang, Hung-Chi; Hung, Cheng-Yu; Ou, Meng-Hsin; Pan, Yi-Yun; Cheng, Mei-Ling; Stern, Arnold; Lo, Szecheng J; Chiu, Daniel Tsun-Yee

2017-01-12

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a commonly pervasive inherited disease in many parts of the world. The complete lack of G6PD activity in a mouse model causes embryonic lethality. The G6PD-deficient Caenorhabditis elegans model also shows embryonic death as indicated by a severe hatching defect. Although increased oxidative stress has been implicated in both cases as the underlying cause, the exact mechanism has not been clearly delineated. In this study with C. elegans, membrane-associated defects, including enhanced permeability, defective polarity and cytokinesis, were found in G6PD-deficient embryos. The membrane-associated abnormalities were accompanied by impaired eggshell structure as evidenced by a transmission electron microscopic study. Such loss of membrane structural integrity was associated with abnormal lipid composition as lipidomic analysis revealed that lysoglycerophospholipids were significantly increased in G6PD-deficient embryos. Abnormal glycerophospholipid metabolism leading to defective embryonic development could be attributed to the increased activity of calcium-independent phospholipase A 2 (iPLA) in G6PD-deficient embryos. This notion is further supported by the fact that the suppression of multiple iPLAs by genetic manipulation partially rescued the embryonic defects in G6PD-deficient embryos. In addition, G6PD deficiency induced disruption of redox balance as manifested by diminished NADPH and elevated lipid peroxidation in embryos. Taken together, disrupted lipid metabolism due to abnormal redox homeostasis is a major factor contributing to abnormal embryonic development in G6PD-deficient C. elegans.

An Analytical Impact Assessment Framework for Wildlife to Inform the Siting and Permitting of Wind Energy Facilities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwartz, Jesse D.M.

In the United States overall electrical generation capacity is expected to increase by 10-25 gigawatts (GW) per year to meet increases in demand. Wind energy is a key component of state and federal renewable energy standards, and central to the Department of Energy’s 20% by 2030 wind production goals. Increased wind energy development may present increased resource conflict with avian wildlife, and environmental permitting has been identified as a potential obstacle to expansion in the sector. ICF developed an analytical framework to help applicants and agencies examine potential impacts in support of facility siting and permitting. A key objective ofmore » our work was to develop a framework that is scalable from the local to the national level, and one that is generalizable across the different scales at which biological communities operate – from local influences to meta-populations. The intent was to allow natural resource managers to estimate the cumulative impacts of turbine strikes and habitat changes on long-term population performance in the context of a species demography, genetic potential, and life history. We developed three types of models based on our literature review and participation in the scientific review processes. First, the conceptual model was developed as a general description of the analytical framework. Second, we developed the analytical framework based on the relationships between concepts, and the functions presented in the scientific literature. Third, we constructed an application of the model by parameterizing the framework using data from and relevant to the Altamont Pass Wind Resource Area (APWRA), and an existing golden eagle population model. We developed managed source code, database create statements, and written documentation to allow for the reproduction of each phase of the analysis. ICF identified a potential template adaptive management system in the form of the US Fish & Wildlife Service (USFWS) Adaptive Harvest Management (AHM) program, and developed recommendations for the structure and function of a similar wind-facility related program. We provided a straw-man implementation of the analytical framework based on assumptions for APWRA-wide golden eagle fatalities, and presented a statistical examination of the model performance. APWRA-wide fatality rates appear substantial at all scales examined from the local APWRA population to the Bird Conservation Region. Documented fatality rates significantly influenced population performance in terms of non-territorial non-breeding birds. Breeder, Juvenile, Subadult, and Adult abundance were mostly unaffected by Baseline APWRA-wide fatality rates. However, increased variability in fatality rates would likely have impacts on long-term population performance, and would result in a substantially larger loss of resources. We developed four recommendations for future study. First, we recommend establishment of concept experts through the existing system of non-profits, regulatory agencies, academia, and industry in the wind energy sector. Second, we recommend the development of a central or distributed shared data repository, and establish guidelines for data sharing and transparency. Third, we recommend development a forum and process for model selection at the local and national level. Last, we recommend experimental implementation of the prescribed system at broader scales, and refinement the expectations for modeling and adaptive management.« less

Iron deficiency anemia

MedlinePlus

Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...