[Coding Causes of Death with IRIS Software. Impact in Navarre Mortality Statistic].

PubMed

Floristán Floristán, Yugo; Delfrade Osinaga, Josu; Carrillo Prieto, Jesus; Aguirre Perez, Jesus; Moreno-Iribas, Conchi

2016-08-02

There are few studies that analyze changes in mortality statistics derived from the use of IRIS software, an automatic system for coding multiple causes of death and for the selection of the underlying cause of death, compared to manual coding. This study evaluated the impact of the use of IRIS in the Navarre mortality statistic. We proceeded to double coding 5,060 death certificates corresponding to residents in Navarra in 2014. We calculated coincidence between the two encodings for ICD10 chapters and for the list of causes of the Spanish National Statistics Institute (INE-102) and we estimated the change on mortality rates. IRIS automatically coded 90% of death certificates. The coincidence to 4 characters and in the same chapter of the CIE10 was 79.1% and 92.0%, respectively. Furthermore, coincidence with the short INE-102 list was 88.3%. Higher matches were found in death certificate of people under 65 years. In comparison with manual coding there was an increase in deaths from endocrine diseases (31%), mental disorders (19%) and disease of nervous system (9%), while a decrease of genitourinary system diseases was observed (21%). The coincidence at level of ICD10 chapters coding by IRIS in comparison to manual coding was 9 out of 10 deaths, similar to what is observed in other studies. The implementation of IRIS has led to increased of endocrine diseases, especially diabetes and hyperlipidaemia, and mental disorders, especially dementias.

High-throughput drug screen identifies chelerythrine as a selective inducer of death in a TSC2-null setting.

PubMed

Medvetz, Doug; Sun, Yang; Li, Chenggang; Khabibullin, Damir; Balan, Murugabaskar; Parkhitko, Andrey; Priolo, Carmen; Asara, John M; Pal, Soumitro; Yu, Jane; Henske, Elizabeth P

2015-01-01

Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress-dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors. This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress-dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. ©2014 American Association for Cancer Research.

Selective Disclosure in a First Conversation about a Family Death in James Agee's Novel "A Death in the Family"

ERIC Educational Resources Information Center

Rober, Peter; Rosenblatt, Paul C.

2013-01-01

The first conversation of a family about a family death is a neglected but potentially important topic. In a first conversation in James Agee's (1957/2006) novel "A Death in the Family," the member who knows the most about the accidental death of another member discloses information selectively. The first conversation in Agee's novel suggests that…

Incidence and fatality of serious suicide attempts in a predominantly rural population in Shandong, China: a public health surveillance study

PubMed Central

Sun, Jiandong; Guo, Xiaolei; Zhang, Jiyu; Wang, Mei; Jia, Cunxian; Xu, Aiqiang

2015-01-01

Objectives To estimate the incidence of serious suicide attempts (SSAs, defined as suicide attempts resulting in either death or hospitalisation) and to examine factors associated with fatality among these attempters. Design A surveillance study of incidence and mortality. Linked data from two public health surveillance systems were analysed. Setting Three selected counties in Shandong, China. Participants All residents in the three selected counties. Outcome measures Incidence rate (per 100 000 person-years) and case fatality rate (%). Methods Records of suicide deaths and hospitalisations that occurred among residents in selected counties during 2009–2011 (5 623 323 person-years) were extracted from electronic databases of the Disease Surveillance Points (DSP) system and the Injury Surveillance System (ISS) and were linked by name, sex, residence and time of suicide attempt. A multiple logistic regression model was developed to examine the factors associated with a higher or lower fatality rate. Results The incidence of SSAs was estimated to be 46 (95% CI 44 to 48) per 100 000 person-years, which was 1.5 times higher in rural versus urban areas, slightly higher among females, and increased with age. Among all SSAs, 51% were hospitalised and survived, 9% were hospitalised but later died and 40% died with no hospitalisation. Most suicide deaths (81%) were not hospitalised and most hospitalised SSAs (85%) survived. The fatality rate was 49% overall, but was significantly higher among attempters living in rural areas, who were male, older, with lower education or with a farming occupation. With regard to the method of suicide, fatality was lowest for non-pesticide poisons (7%) and highest for hanging (97%). Conclusions The incidence of serious suicide attempts is substantially higher in rural areas than in urban areas of China. The risk of death is influenced by the attempter's sex, age, education level, occupation, method used and season of year. PMID:25673439

Evolutionary games on cycles with strong selection

NASA Astrophysics Data System (ADS)

Altrock, P. M.; Traulsen, A.; Nowak, M. A.

2017-02-01

Evolutionary games on graphs describe how strategic interactions and population structure determine evolutionary success, quantified by the probability that a single mutant takes over a population. Graph structures, compared to the well-mixed case, can act as amplifiers or suppressors of selection by increasing or decreasing the fixation probability of a beneficial mutant. Properties of the associated mean fixation times can be more intricate, especially when selection is strong. The intuition is that fixation of a beneficial mutant happens fast in a dominance game, that fixation takes very long in a coexistence game, and that strong selection eliminates demographic noise. Here we show that these intuitions can be misleading in structured populations. We analyze mean fixation times on the cycle graph under strong frequency-dependent selection for two different microscopic evolutionary update rules (death-birth and birth-death). We establish exact analytical results for fixation times under strong selection and show that there are coexistence games in which fixation occurs in time polynomial in population size. Depending on the underlying game, we observe inherence of demographic noise even under strong selection if the process is driven by random death before selection for birth of an offspring (death-birth update). In contrast, if selection for an offspring occurs before random removal (birth-death update), then strong selection can remove demographic noise almost entirely.

Death Rate of Dental Anaesthesia

PubMed Central

Mortazavi, Hamed; Safi, Yaser

2017-01-01

Death was the most important side effect of anaesthesia in dentistry. In this article we reviewed more than 20 studies with adequate data focusing on death associated with dental procedures since 1955 and found 218 deaths out of 71,435,282 patients (3 deaths per 1,000,000 persons) with the mortality rate of 1:327,684. In addition, mortality rate per million has dropped to half (6.2 per 1,000,000 vs. 3 per 1,000,000) since 1955 till the last report in 2012 without any sex predilection. In children, most cases died in the age of two to five years. Hypoxia was the most common cause of death, and cardiovascular, respiratory, and endocrine disorders, hepatic cirrhosis, septicaemia, and bacterial endocarditis were the most frequent underlying systemic disease in deceased patients. Although rare death following general anaesthesia in dentistry, is a critical side effect mostly seen in patients with compromised health condition. Therefore, appropriate case selection in regard with patients’ general health status as well as standard technical and equipment conditions are mandatory to diminish the risk of death during dental anaesthesia. PMID:28764309

The sex-selective impact of the Black Death and recurring plagues in the Southern Netherlands, 1349-1450.

PubMed

Curtis, Daniel R; Roosen, Joris

2017-10-01

Although recent work has begun to establish that early modern plagues had selective mortality effects, it was generally accepted that the initial outbreak of Black Death in 1347-52 was a "universal killer." Recent bioarchaeological work, however, has argued that the Black Death was also selective with regard to age and pre-plague health status. The issue of the Black Death's potential sex selectivity is less clear. Bioarchaeological research hypothesizes that sex-selection in mortality was possible during the initial Black Death outbreak, and we present evidence from historical sources to test this notion. To determine whether the Black Death and recurring plagues in the period 1349-1450 had a sex-selective mortality effect. We present a newly compiled database of mortality information taken from mortmain records in Hainaut, Belgium, in the period 1349-1450, which not only is an important new source of information on medieval mortality, but also allows for sex-disaggregation. We find that the Black Death period of 1349-51, as well as recurring plagues in the 100 years up to 1450, often had a sex-selective effect-killing more women than in "non-plague years." Although much research tends to suggest that men are more susceptible to a variety of diseases caused by bacteria, viruses and parasites, we cannot assume that the same direction of sex-selection in mortality applied to diseases in the distant past such as Second Pandemic plagues. While the exact reasons for the sex-selective effect of late-medieval plague are unclear in the absence of further data, we suggest that simple inequities between the sexes in exposure to the disease may not have been a key driver. © 2017 Wiley Periodicals, Inc.

Antioxidant gene therapy against neuronal cell death

PubMed Central

Navarro-Yepes, Juliana; Zavala-Flores, Laura; Annadurai, Anandhan; Wang, Fang; Skotak, Maciej; Chandra, Namas; Li, Ming; Pappa, Aglaia; Martinez-Fong, Daniel; Razo, Luz Maria Del; Quintanilla-Vega, Betzabet; Franco, Rodrigo

2014-01-01

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated in mitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy. PMID:24333264

Colourful death: six-parameter classification of cell death by flow cytometry--dead cells tell tales.

PubMed

Munoz, Luis E; Maueröder, Christian; Chaurio, Ricardo; Berens, Christian; Herrmann, Martin; Janko, Christina

2013-08-01

The response of the immune system against dying and dead cells strongly depends on the cell death phenotype. Beside other forms of cell death, two clearly distinct populations, early apoptotic and secondary necrotic cells, have been shown to induce anti-inflammation/tolerance and inflammation/immune priming, respectively. Cytofluorometry is a powerful technique to detect morphological and phenotypical changes occurring during cell death. Here, we describe a new technique using AnnexinA5, propidiumiodide, DiIC1(5) and Hoechst 33342 to sub-classify populations of apoptotic and/or necrotic cells. The method allows the fast and reliable identification of several different phases and pathways of cell death by analysing the following cell death associated changes in a single tube: cellular granularity and shrinkage, phosphatidylserine exposure, ion selectivity of the plasma membrane, mitochondrial membrane potential, and DNA content. The clear characterisation of cell death is of major importance for instance in immunization studies, in experimental therapeutic settings, and in the exploration of cell-death associated diseases. It also enables the analysis of immunological properties of distinct populations of dying cells and the pathways involved in this process.

The hnRNP-Htt axis regulates necrotic cell death induced by transcriptional repression through impaired RNA splicing.

PubMed

Mao, Y; Tamura, T; Yuki, Y; Abe, D; Tamada, Y; Imoto, S; Tanaka, H; Homma, H; Tagawa, K; Miyano, S; Okazawa, H

2016-04-28

In this study, we identify signaling network of necrotic cell death induced by transcriptional repression (TRIAD) by α-amanitin (AMA), the selective RNA polymerase II inhibitor, as a model of neurodegenerative cell death. We performed genetic screen of a knockdown (KD) fly library by measuring the ratio of transformation from pupa to larva (PL ratio) under TRIAD, and selected the cell death-promoting genes. Systems biology analysis of the positive genes mapped on protein-protein interaction databases predicted the signaling network of TRIAD and the core pathway including heterogeneous nuclear ribonucleoproteins (hnRNPs) and huntingtin (Htt). RNA sequencing revealed that AMA impaired transcription and RNA splicing of Htt, which is known as an endoplasmic reticulum (ER)-stabilizing molecule. The impairment in RNA splicing and PL ratio was rescued by overexpresion of hnRNP that had been also affected by transcriptional repression. Fly genetics with suppressor or expresser of Htt and hnRNP worsened or ameliorated the decreased PL ratio by AMA, respectively. Collectively, these results suggested involvement of RNA splicing and a regulatory role of the hnRNP-Htt axis in the process of the transcriptional repression-induced necrosis.

Using National Inpatient Death Rates as a Benchmark to Identify Hospitals with Inaccurate Cause of Death Reporting - Missouri, 2009-2012.

PubMed

Lloyd, Jennifer; Jahanpour, Ehsan; Angell, Brian; Ward, Craig; Hunter, Andy; Baysinger, Cherri; Turabelidze, George

2017-01-13

Reporting causes of death accurately is essential to public health and hospital-based programs; however, some U.S. studies have identified substantial inaccuracies in cause of death reporting. Using CDC's national inpatient hospital death rates as a benchmark, the Missouri Department of Health and Senior Services (DHSS) analyzed inpatient death rates reported by hospitals with high inpatient death rates in St. Louis and Kansas City metro areas. Among the selected hospitals with high inpatient death rates, 45.8% of death certificates indicated an underlying cause of death that was inconsistent with CDC's Guidelines for Death Certificate completion. Selected hospitals with high inpatient death rates were more likely to overreport heart disease and renal disease, and underreport cancer as an underlying cause of death. Based on these findings, the Missouri DHSS initiated a new web-based training module for death certificate completion based on the CDC guidelines in an effort to improve accuracy in cause of death reporting.

Uncoupling phototoxicity-elicited neural dysmorphology and death by insidious function and selective impairment of Ran-binding protein 2 (Ranbp2).

PubMed

Cho, Kyoung-in; Haney, Victoria; Yoon, Dosuk; Hao, Yin; Ferreira, Paulo A

2015-12-21

Morphological disintegration of neurons is coupled invariably to neural death. In particular, disruption of outer segments of photoreceptor neurons triggers photoreceptor death regardless of the pathological stressors. We show that Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) mice with mutations in SUMO-binding motif (SBM) of cyclophilin-like domain (CLD) of Ran-binding protein 2 (Ranbp2) expressed in a null Ranbp2 background lack untoward effects in photoreceptors in the absence of light-stress. However, compared to wild type photoreceptors, light-stress elicits profound disintegration of outer segments of Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) with paradoxical age-dependent resistance of photoreceptors to death and genotype-independent activation of caspases. Ranbp2(-/-)::Tg-Ranbp2(CLDm-HA) exhibit photoreceptor death-independent changes in ubiquitin-proteasome system (UPS), but death-dependent increase of ubiquitin carrier protein 9(ubc9) levels. Hence, insidious functional impairment of SBM of Ranbp2's CLD promotes neuroprotection and uncoupling of photoreceptor degeneration and death against phototoxicity. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

EMT-defibrillation: a recipe for saving lives.

PubMed

Paris, P M

1988-05-01

Sudden cardiac death is the number-one cause of death in this country. It has long been known that most of these deaths occur outside of the hospital, therefore necessitating an approach to the problem involving prehospital care. The development of advanced life support emergency medical systems has had a dramatic impact on improving survival in selected communities. Most of the country continues to see little result because of our inability to provide timely defibrillation. Automatic external defibrillators now provide a safe, reliable, proven method to increase the number of "saves" in rural, urban, and suburban communities. This new tool, if widely used, will allow us to save scores of "hearts too good to die."

Sensitivity and specificity of administrative mortality data for identifying prescription opioid–related deaths

PubMed Central

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G.; Fernandes, Kimberly A.; Martins, Diana; Gomes, Tara

2016-01-01

Background: Comprehensive systems for surveilling prescription opioid–related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid–related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid–related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. Methods: We identified all prescription opioid–related deaths from Ontario coroners’ data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid–related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid–related deaths. Results: Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. Interpretation: In the absence of specific systems for monitoring prescription opioid–related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid–related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. PMID:26622006

Sensitivity and specificity of administrative mortality data for identifying prescription opioid-related deaths.

PubMed

Gladstone, Emilie; Smolina, Kate; Morgan, Steven G; Fernandes, Kimberly A; Martins, Diana; Gomes, Tara

2016-03-01

Comprehensive systems for surveilling prescription opioid-related harms provide clear evidence that deaths from prescription opioids have increased dramatically in the United States. However, these harms are not systematically monitored in Canada. In light of a growing public health crisis, accessible, nationwide data sources to examine prescription opioid-related harms in Canada are needed. We sought to examine the performance of 5 algorithms to identify prescription opioid-related deaths from vital statistics data against data abstracted from the Office of the Chief Coroner of Ontario as a gold standard. We identified all prescription opioid-related deaths from Ontario coroners' data that occurred between Jan. 31, 2003, and Dec. 31, 2010. We then used 5 different algorithms to identify prescription opioid-related deaths from vital statistics death data in 2010. We selected the algorithm with the highest sensitivity and a positive predictive value of more than 80% as the optimal algorithm for identifying prescription opioid-related deaths. Four of the 5 algorithms had positive predictive values of more than 80%. The algorithm with the highest sensitivity (75%) in 2010 improved slightly in its predictive performance from 2003 to 2010. In the absence of specific systems for monitoring prescription opioid-related deaths in Canada, readily available national vital statistics data can be used to study prescription opioid-related mortality with considerable accuracy. Despite some limitations, these data may facilitate the implementation of national surveillance and monitoring strategies. © 2016 Canadian Medical Association or its licensors.

Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination.

PubMed

Linden, Jennifer R; Ma, Yinghua; Zhao, Baohua; Harris, Jason Michael; Rumah, Kareem Rashid; Schaeren-Wiemers, Nicole; Vartanian, Timothy

2015-06-16

Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody. Our intestinal tract is host to trillions of microorganisms that play an essential role in health and homeostasis. Disruption of this symbiotic relationship has been implicated in influencing or causing disease in distant organ systems such as the brain. Epsilon toxin (ε-toxin)-carrying Clostridium perfringens strains are responsible for a devastating white matter disease in ruminant animals that shares similar features with human multiple sclerosis. In this report, we define the mechanism by which ε-toxin causes white matter disease. We find that ε-toxin specifically targets the myelin-forming cells of the central nervous system (CNS), oligodendrocytes, leading to cell death. The selectivity of ε-toxin for oligodendrocytes is remarkable, as other cells of the CNS are unaffected. Importantly, ε-toxin-induced oligodendrocyte death results in demyelination and is dependent on expression of myelin and lymphocyte protein (MAL). These results help complete the mechanistic pathway from bacteria to brain by explaining the specific cellular target of ε-toxin within the CNS. Copyright © 2015 Linden et al.

From surveillance to action: early gains from the National Violent Death Reporting System.

PubMed

Campbell, R; Weis, M A; Millet, L; Powell, V; Hull-Jilly, D; Hackman, H

2006-12-01

Drawing from the experiences of individual state programs that currently participate in the National Violent Death Reporting System (NVDRS), this article reviews some of the practical benefits that may accrue from the introduction of violent death surveillance systems. As a state-based surveillance system that uses multiple data sources and relies upon multiple stakeholders, the NVDRS program has fostered an array of initiatives within and among individual state programs. State-based initiatives highlighted in this article were selected on the basis of a purposive sampling strategy intended to illustrate key aspects of program development. The NVDRS state programs are in Alaska, California, Colorado, Georgia, Kentucky, Maryland, Massachusetts, New Jersey, New Mexico, North Carolina, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin. The NVDRS has helped to build alliances and collaborative efforts between key stakeholders, facilitated the recognition of violent death as a public health problem through outreach and media attention, acted as a catalyst for new projects, enhanced surveillance of special populations and utility for evaluation, and identified key circumstances that will target interventions in state prevention planning. The NVDRS has implemented data collection efforts and is beginning to produce and analyze findings. In the process of implementing the data collection system and publicizing findings, state NVDRS programs are realizing other gains that strengthen their surveillance efforts. The use of data for prevention purposes will be the ultimate indicator of program success.

Stochastic evolutionary voluntary public goods game with punishment in a Quasi-birth-and-death process.

PubMed

Quan, Ji; Liu, Wei; Chu, Yuqing; Wang, Xianjia

2017-11-23

Traditional replication dynamic model and the corresponding concept of evolutionary stable strategy (ESS) only takes into account whether the system can return to the equilibrium after being subjected to a small disturbance. In the real world, due to continuous noise, the ESS of the system may not be stochastically stable. In this paper, a model of voluntary public goods game with punishment is studied in a stochastic situation. Unlike the existing model, we describe the evolutionary process of strategies in the population as a generalized quasi-birth-and-death process. And we investigate the stochastic stable equilibrium (SSE) instead. By numerical experiments, we get all possible SSEs of the system for any combination of parameters, and investigate the influence of parameters on the probabilities of the system to select different equilibriums. It is found that in the stochastic situation, the introduction of the punishment and non-participation strategies can change the evolutionary dynamics of the system and equilibrium of the game. There is a large range of parameters that the system selects the cooperative states as its SSE with a high probability. This result provides us an insight and control method for the evolution of cooperation in the public goods game in stochastic situations.

The Birth-Death-Mutation Process: A New Paradigm for Fat Tailed Distributions

PubMed Central

Maruvka, Yosef E.; Kessler, David A.; Shnerb, Nadav M.

2011-01-01

Fat tailed statistics and power-laws are ubiquitous in many complex systems. Usually the appearance of of a few anomalously successful individuals (bio-species, investors, websites) is interpreted as reflecting some inherent “quality” (fitness, talent, giftedness) as in Darwin's theory of natural selection. Here we adopt the opposite, “neutral”, outlook, suggesting that the main factor explaining success is merely luck. The statistics emerging from the neutral birth-death-mutation (BDM) process is shown to fit marvelously many empirical distributions. While previous neutral theories have focused on the power-law tail, our theory economically and accurately explains the entire distribution. We thus suggest the BDM distribution as a standard neutral model: effects of fitness and selection are to be identified by substantial deviations from it. PMID:22069453

Drop or fly? Negative genetic correlation between death-feigning intensity and flying ability as alternative anti-predator strategies

PubMed Central

Ohno, Tatsunori; Miyatake, Takahisa

2006-01-01

A prey animal may have the alternative of flying away or feigning death when it encounters predators. These alternatives have a genetic base as anti-predator strategies in the adzuki bean beetle, Callosobruchus chinensis. A negative genetic correlation between death-feigning intensity and flying ability was found in C. chinensis, i.e. lower flying ability is genetically connected to escaping by dropping from a perch and then feigning death, whereas higher flying ability does not correspond to death-feigning behaviour. Two bidirectional artificial selections for death-feigning duration and flying ability were conducted independently in C. chinensis. The strains selected for shorter (longer) duration of death-feigning had higher (lower) flying ability, while the strains selected for lower (higher) flying ability showed longer (shorter) duration of death-feigning. When the two traits were compared in 21 populations of C. chinensis derived from different geographical regions, a significant negative correlation was found between death-feigning intensity and flying ability. Based on these results, the choice between alternative escaping behaviours in animals is discussed from two points of view: phenotypic plasticity, an individual with two tactics; and pleiotropic genetic correlation, different individuals with opposite strategies. PMID:17476776

Counting every stillbirth and neonatal death through mortality audit to improve quality of care for every pregnant woman and her baby.

PubMed

Kerber, Kate J; Mathai, Matthews; Lewis, Gwyneth; Flenady, Vicki; Erwich, Jan Jaap H M; Segun, Tunde; Aliganyira, Patrick; Abdelmegeid, Ali; Allanson, Emma; Roos, Nathalie; Rhoda, Natasha; Lawn, Joy E; Pattinson, Robert

2015-01-01

While there is widespread acknowledgment of the need for improved quality and quantity of information on births and deaths, there has been less movement towards systematically capturing and reviewing the causes and avoidable factors linked to deaths, in order to affect change. This is particularly true for stillbirths and neonatal deaths which can fall between different health care providers and departments. Maternal and perinatal mortality audit applies to two of the five objectives in the Every Newborn Action Plan but data on successful approaches to overcome bottlenecks to scaling up audit are lacking. We reviewed the current evidence for facility-based perinatal mortality audit with a focus on low- and middle-income countries and assessed the status of mortality audit policy and implementation. Based on challenges identified in the literature, key challenges to completing the audit cycle and affecting change were identified across the WHO health system building blocks, along with solutions, in order to inform the process of scaling up this strategy with attention to quality. Maternal death surveillance and review is moving rapidly with many countries enacting and implementing policies and with accountability beyond the single facility conducting the audits. While 51 priority countries report having a policy on maternal death notification in 2014, only 17 countries have a policy for reporting and reviewing stillbirths and neonatal deaths. The existing evidence demonstrates the potential for audit to improve birth outcomes, only if the audit cycle is completed. The primary challenges within the health system building blocks are in the area of leadership and health information. Examples of successful implementation exist from high income countries and select low- and middle-income countries provide valuable learning, especially on the need for leadership for effective audit systems and on the development and the use of clear guidelines and protocols in order to ensure that the audit cycle is completed. Health workers have the power to change health care routines in daily practice, but this must be accompanied by concrete inputs at every level of the health system. The system requires data systems including consistent cause of death classification and use of best practice guidelines to monitor performance, as well as leaders to champion the process, especially to ensure a no-blame environment, and to access change agents at other levels to address larger, systemic challenges.

Did death certificates and a death review process agree on lung cancer cause of death in the National Lung Screening Trial?

PubMed

Marcus, Pamela M; Doria-Rose, Vincent Paul; Gareen, Ilana F; Brewer, Brenda; Clingan, Kathy; Keating, Kristen; Rosenbaum, Jennifer; Rozjabek, Heather M; Rathmell, Joshua; Sicks, JoRean; Miller, Anthony B

2016-08-01

Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer. Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death. In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as compared with the published finding of 20% (95% confidence interval: 6.7-26.7). Death review may not be necessary for primary-outcome analyses in lung cancer screening trials. If deemed necessary, researchers should strive to streamline the death review process as much as possible. © The Author(s) 2016.

Autonomous rexinoid death signaling is suppressed by converging signaling pathways in immature leukemia cells.

PubMed

Benoit, G R; Flexor, M; Besançon, F; Altucci, L; Rossin, A; Hillion, J; Balajthy, Z; Legres, L; Ségal-Bendirdjian, E; Gronemeyer, H; Lanotte, M

2001-07-01

On their own, retinoid X receptor (RXR)-selective ligands (rexinoids) are silent in retinoic acid receptor (RAR)-RXR heterodimers, and no selective rexinoid program has been described as yet in cellular systems. We report here on the rexinoid signaling capacity that triggers apoptosis of immature promyelocytic NB4 cells as a default pathway in the absence of survival factors. Rexinoid-induced apoptosis displays all features of bona fide programmed cell death and is inhibited by RXR, but not RAR antagonists. Several types of survival signals block rexinoid-induced apoptosis. RARalpha agonists switch the cellular response toward differentiation and induce the expression of antiapoptosis factors. Activation of the protein kinase A pathway in the presence of rexinoid agonists induces maturation and blocks immature cell apoptosis. Addition of nonretinoid serum factors also blocks cell death but does not induce cell differentiation. Rexinoid-induced apoptosis is linked to neither the presence nor stability of the promyelocytic leukemia-RARalpha fusion protein and operates also in non-acute promyelocytic leukemia cells. Together our results support a model according to which rexinoids activate in certain leukemia cells a default death pathway onto which several other signaling paradigms converge. This pathway is entirely distinct from that triggered by RAR agonists, which control cell maturation and postmaturation apoptosis.

Harnessing tumor necrosis factor receptors to enhance antitumor activities of drugs.

PubMed

Muntané, Jordi

2011-10-17

Cancer is the second-leading cause of death in the U.S. behind heart disease and over stroke. The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The inhibition of cell death pathways is one of these tumor characteristics which also include sustained proliferative signaling, evading growth suppressor signaling, replicative immortality, angiogenesis, and promotion of invasion and metastasis. Cell death is mediated through death receptor (DR) stimulation initiated by specific ligands that transmit signaling to the cell death machinery or through the participation of mitochondria. Cell death involving DR is mediated by the superfamily of tumor necrosis factor receptor (TNF-R) which includes TNF-R type I, CD95, DR3, TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 (TRAIL-R1) and -2 (TRAIL-R2), DR6, ectodysplasin A (EDA) receptor (EDAR), and the nerve growth factor (NGF) receptor (NGFR). The expression of these receptors in healthy and tumor cells induces treatment side effects that limit the systemic administration of cell death-inducing therapies. The present review is focused on the different therapeutic strategies such as targeted antibodies or small molecules addressed to selective stimulated DR-mediated apoptosis or reduce cell proliferation in cancer cells.

Excitotoxicity-induced prostaglandin D2 production induces sustained microglial activation and delayed neuronal death.

PubMed

Iwasa, Kensuke; Yamamoto, Shinji; Yagishita, Sosuke; Maruyama, Kei; Yoshikawa, Keisuke

2017-04-01

Excitotoxicity is the pivotal mechanism of neuronal death. Prostaglandins (PGs) produced during excitotoxicity play important roles in neurodegenerative conditions. Previously, we demonstrated that initial burst productions of PGD 2 , PGE 2 , and PGF 2α are produced by cyclooxygenase-2 (COX-2) in the hippocampus following a single systemic kainic acid (KA) administration. In addition, we showed that blocking of all PG productions ameliorated hippocampal delayed neuronal death at 30 days after KA administration. To investigate the role of individual PGs in the delayed neuronal death, we performed intracerebroventricular injection of PGD 2 , PGE 2 , or PGF 2α in rats whose hippocampal PG productions were entirely blocked by pretreatment of NS398, a COX-2 selective inhibitor. Administration of PGD 2 and PGF 2α had a latent contribution to the delayed neuronal death, sustained over 30 days after a single KA treatment. Furthermore, PGD 2 enhanced microglial activation, which may be involved in the delayed neuronal death in the hippocampus. These findings suggest that excitotoxic delayed neuronal death is mediated through microglia activated by PGD 2 . Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Non-apoptotic cell death in animal development.

PubMed

Kutscher, Lena M; Shaham, Shai

2017-08-01

Programmed cell death (PCD) is an important process in the development of multicellular organisms. Apoptosis, a form of PCD characterized morphologically by chromatin condensation, membrane blebbing, and cytoplasm compaction, and molecularly by the activation of caspase proteases, has been extensively investigated. Studies in Caenorhabditis elegans, Drosophila, mice, and the developing chick have revealed, however, that developmental PCD also occurs through other mechanisms, morphologically and molecularly distinct from apoptosis. Some non-apoptotic PCD pathways, including those regulating germ cell death in Drosophila, still appear to employ caspases. However, another prominent cell death program, linker cell-type death (LCD), is morphologically conserved, and independent of the key genes that drive apoptosis, functioning, at least in part, through the ubiquitin proteasome system. These non-apoptotic processes may serve as backup programs when caspases are inactivated or unavailable, or, more likely, as freestanding cell culling programs. Non-apoptotic PCD has been documented extensively in the developing nervous system, and during the formation of germline and somatic gonadal structures, suggesting that preservation of these mechanisms is likely under strong selective pressure. Here, we discuss our current understanding of non-apoptotic PCD in animal development, and explore possible roles for LCD and other non-apoptotic developmental pathways in vertebrates. We raise the possibility that during vertebrate development, apoptosis may not be the major PCD mechanism.

The Effectiveness of Child Restraint Systems for Children Aged 3 Years or Younger During Motor Vehicle Collisions: 1996 to 2005

PubMed Central

Anderson, Craig L.

2009-01-01

Objectives. We estimated the effectiveness of child restraints in preventing death during motor vehicle collisions among children 3 years or younger. Methods. We conducted a matched cohort study using Fatality Analysis Reporting System data from 1996 to 2005. We estimated death risk ratios using conditional Poisson regression, bootstrapping, multiple imputation, and a sensitivity analysis of misclassification bias. We examined possible effect modification by selected factors. Results. The estimated death risk ratios comparing child safety seats with no restraint were 0.27 (95% confidence interval [CI] = 0.21, 0.34) for infants, 0.24 (95% CI = 0.19, 0.30) for children aged 1 year, 0.40 (95% CI = 0.32, 0.51) for those aged 2 years, and 0.41 (95% CI = 0.33, 0.52) for those aged 3 years. Estimated safety seat effectiveness was greater during rollover collisions, in rural environments, and in light trucks. We estimated seat belts to be as effective as safety seats in preventing death for children aged 2 and 3 years. Conclusions. Child safety seats are highly effective in reducing the risk of death during severe traffic collisions and generally outperform seat belts. Parents should be encouraged to use child safety seats in favor of seat belts. PMID:19059860

Nonequivalence of updating rules in evolutionary games under high mutation rates.

PubMed

Kaiping, G A; Jacobs, G S; Cox, S J; Sluckin, T J

2014-10-01

Moran processes are often used to model selection in evolutionary simulations. The updating rule in Moran processes is a birth-death process, i. e., selection according to fitness of an individual to give birth, followed by the death of a random individual. For well-mixed populations with only two strategies this updating rule is known to be equivalent to selecting unfit individuals for death and then selecting randomly for procreation (biased death-birth process). It is, however, known that this equivalence does not hold when considering structured populations. Here we study whether changing the updating rule can also have an effect in well-mixed populations in the presence of more than two strategies and high mutation rates. We find, using three models from different areas of evolutionary simulation, that the choice of updating rule can change model results. We show, e. g., that going from the birth-death process to the death-birth process can change a public goods game with punishment from containing mostly defectors to having a majority of cooperative strategies. From the examples given we derive guidelines indicating when the choice of the updating rule can be expected to have an impact on the results of the model.

Nonequivalence of updating rules in evolutionary games under high mutation rates

NASA Astrophysics Data System (ADS)

Kaiping, G. A.; Jacobs, G. S.; Cox, S. J.; Sluckin, T. J.

2014-10-01

Moran processes are often used to model selection in evolutionary simulations. The updating rule in Moran processes is a birth-death process, i. e., selection according to fitness of an individual to give birth, followed by the death of a random individual. For well-mixed populations with only two strategies this updating rule is known to be equivalent to selecting unfit individuals for death and then selecting randomly for procreation (biased death-birth process). It is, however, known that this equivalence does not hold when considering structured populations. Here we study whether changing the updating rule can also have an effect in well-mixed populations in the presence of more than two strategies and high mutation rates. We find, using three models from different areas of evolutionary simulation, that the choice of updating rule can change model results. We show, e. g., that going from the birth-death process to the death-birth process can change a public goods game with punishment from containing mostly defectors to having a majority of cooperative strategies. From the examples given we derive guidelines indicating when the choice of the updating rule can be expected to have an impact on the results of the model.

Mortality of People with Intellectual and Developmental Disabilities from Select US State Disability Service Systems and Medical Claims Data.

PubMed

Lauer, Emily; McCallion, Philip

2015-09-01

Monitoring population trends including mortality within subgroups such as people with intellectual and developmental disabilities and between countries provides crucial information about the population's health and insights into underlying health concerns and the need for and effectiveness of public health efforts. Data from both US state intellectual and developmental disabilities service system administrative data sets and de-identified state Medicaid claims were used to calculate average age at death and crude mortality rates. Average age at death for people in state intellectual and developmental disabilities systems was 50.4-58.7 years and 61.2-63.0 years in Medicaid data, with a crude adult mortality rate of 15.2 per thousand. Age at death remains lower and mortality rates higher for people with intellectual and developmental disabilities. Improved case finding (e.g. medical claims) could provide more complete mortality patterns for the population with intellectual and developmental disabilities to inform the range of access and receipt of supportive and health-related interventions and preventive care. © 2015 John Wiley & Sons Ltd.

Occupational Homicides of Law Enforcement Officers, 2003-2013: Data From the National Violent Death Reporting System.

PubMed

Blair, Janet M; Fowler, Katherine A; Betz, Carter J; Baumgardner, Jason L

2016-11-01

Law enforcement officers (LEOs) in the U.S. are at an increased risk for homicide. The purpose of this study is to describe the characteristics of homicides of LEOs in 17 U.S. states participating in the National Violent Death Reporting System. This active surveillance system uses data from death certificates, coroner/medical examiner reports, and law enforcement reports. This study used quantitative and qualitative methods to analyze National Violent Death Reporting System data for 2003-2013. Deaths of LEOs feloniously killed in the line of duty were selected for analysis. LEO homicides and the circumstances preceding or occurring during the incident were characterized. Analyses were conducted October 2015-June 2016. A total of 128 officer homicides from 121 incidents were identified. Most (93.7%) LEO victims were male, 60.9% were aged 30-49 years (average age, 40.9 years). Approximately 21.9% of LEOs were killed during an ambush, and 19.5% were killed during traffic stops or pursuits. Of the 14.1% of LEOs killed responding to domestic disturbances, most disturbances were intimate partner violence related. More than half (57.0%) of homicides were precipitated by another crime, and of these, 71.2% involved crimes in progress. Most suspects were male. Ninety-one percent of homicides of LEOs were committed with a firearm. This information is critical to help describe encounter situations faced by LEOs. The results of this study can be used to help educate and train LEOs on hazards, inform prevention efforts designed to promote LEO safety, and prevent homicide among this population. Published by Elsevier Inc.

Angiotensin II potentiates zinc-induced cortical neuronal death by acting on angiotensin II type 2 receptor.

PubMed

Park, Mi-Ha; Kim, Ha Na; Lim, Joon Seo; Ahn, Jae-Sung; Koh, Jae-Young

2013-12-01

The angiotensin system has several non-vascular functions in the central nervous system. For instance, inhibition of the brain angiotensin system results in a reduction in neuronal death following acute brain injury such as ischemia and intracerebral hemorrhage, even under conditions of constant blood pressure. Since endogenous zinc has been implicated as a key mediator of ischemic neuronal death, we investigated the possibility that the angiotensin system affects the outcome of zinc-triggered neuronal death in cortical cell cultures. Exposure of cortical cultures containing neurons and astrocytes to 300 μM zinc for 15 min induced submaximal death in both types of cells. Interestingly, addition of angiotensin II significantly enhanced the zinc-triggered neuronal death, while leaving astrocytic cell death relatively unchanged. Both type 1 and 2 angiotensin II receptors (AT1R and AT2R, respectively) were expressed in neurons as well as astrocytes. Zinc neurotoxicity was substantially attenuated by PD123319, a specific inhibitor of AT2R, and augmented by CGP42112, a selective activator of AT2R, indicating a critical role for this receptor subtype in the augmentation of neuronal cell death.Because zinc toxicity occurs largely through oxidative stress, the levels of superoxides in zinc-treated neurons were assessed by DCF fluorescence microscopy. Combined treatment with zinc and angiotensin II substantially increased the levels of superoxides in neurons compared to those induced by zinc alone. This increase in oxidative stress by angiotensin II was completely blocked by the addition of PD123319. Finally, since zinc-induced oxidative stress may be caused by induction and/or activation of NADPH oxidase, the activation status of Rac and the level of the NADPH oxidase subunit p67phox were measured. Angiotensin II markedly increased Rac activity and the levels of p67phox in zinc-treated neurons and astrocytes in a PD123319-dependent manner. The present study shows that the angiotensin system, especially that involving AT2R, may have an oxidative injury-potentiating effect via augmentation of the activity of NADPH oxidase. Hence, blockade of angiotensin signaling cascades in the brain may prove useful in protecting against the oxidative neuronal death that is likely to occur in acute brain injury.

Evolution: the dialogue between life and death

NASA Astrophysics Data System (ADS)

Holliday, robin

1997-12-01

Organisms have the ability to harness energy from the environment to create order and to reproduce. From early error-prone systems natural selection acted to produce present day organisms with high accuracy in the synthesis of macromolecules. The environment imposes strict limits on reproduction, so evolution is always accompanied by the discarding of a large proportion of the less fit cells, or organisms. Sexual reproduction depends on an immortal germline and a soma which may be immortal or mortal. Higher animals living in hazardous environments have evolved aging and death of the soma for the benefit of the ongoing germline.

What cell death does in development.

PubMed

Zakeri, Zahra; Penaloza, Carlos G; Smith, Kyle; Ye, Yixia; Lockshin, Richard A

2015-01-01

Cell death is prominent in gametogenesis and shapes and sculpts embryos. In non-mammalian embryos one sees little or no cell death prior to the maternal-zygotic transition, but, in mammalian embryos, characteristic deaths of one or two cells occur at the end of compaction and are apparently necessary for the separation of the trophoblast from the inner cell mass. Considerable sculpting of the embryo occurs by cell deaths during organogenesis, and appropriate cell numbers, especially in the CNS and in the immune system, are generated by massive overproduction of cells and selection of a few, with death of the rest. The timing, identity, and genetic control of specific cells that die have been well documented in Caenorhabditis, but in other embryos the stochastic nature of the deaths limit our ability to do more than identify the regions in which cells will die. Complete disruption of the cell death machinery can be lethal, but many mutations of the regulatory machinery yield only modest or no phenotypes, indicating substantial redundancy and compensation of regulatory mechanisms. Most of the deaths are apoptotic and are identified by techniques used to recognize apoptosis, but techniques identifying lysosomes (whether in dying or involuting cells or in the phagocytes that invade the tissue) also reveal patterns of cell death. Aberrant cell deaths that produce known phenotypes are typically localized, indicating that the mechanism of activating a programmed death in a specific region, rather than the mechanism of death, is aberrant. These results lead us to conclude that we need to know much more about the conversations among cells that lead cells to commit suicide.

Health gains and financial risk protection afforded by public financing of selected interventions in Ethiopia: an extended cost-effectiveness analysis.

PubMed

Verguet, Stéphane; Olson, Zachary D; Babigumira, Joseph B; Desalegn, Dawit; Johansson, Kjell Arne; Kruk, Margaret E; Levin, Carol E; Nugent, Rachel A; Pecenka, Clint; Shrime, Mark G; Memirie, Solomon Tessema; Watkins, David A; Jamison, Dean T

2015-05-01

The way in which a government chooses to finance a health intervention can affect the uptake of health interventions and consequently the extent of health gains. In addition to health gains, some policies such as public finance can insure against catastrophic health expenditures. We aimed to evaluate the health and financial risk protection benefits of selected interventions that could be publicly financed by the government of Ethiopia. We used extended cost-effectiveness analysis to assess the health gains (deaths averted) and financial risk protection afforded (cases of poverty averted) by a bundle of nine (among many other) interventions that the Government of Ethiopia aims to make universally available. These nine interventions were measles vaccination, rotavirus vaccination, pneumococcal conjugate vaccination, diarrhoea treatment, malaria treatment, pneumonia treatment, caesarean section surgery, hypertension treatment, and tuberculosis treatment. Our analysis shows that, per dollar spent by the Ethiopian Government, the interventions that avert the most deaths are measles vaccination (367 deaths averted per $100,000 spent), pneumococcal conjugate vaccination (170 deaths averted per $100,000 spent), and caesarean section surgery (141 deaths averted per $100,000 spent). The interventions that avert the most cases of poverty are caesarean section surgery (98 cases averted per $100,000 spent), tuberculosis treatment (96 cases averted per $100,000 spent), and hypertension treatment (84 cases averted per $100,000 spent). Our approach incorporates financial risk protection into the economic evaluation of health interventions and therefore provides information about the efficiency of attainment of both major objectives of a health system: improved health and financial risk protection. One intervention might rank higher on one or both metrics than another, which shows how intervention choice-the selection of a pathway to universal health coverage-might involve weighing up of sometimes competing objectives. This understanding can help policy makers to select interventions to target specific policy goals (ie, improved health or financial risk protection). It is especially relevant for the design and sequencing of universal health coverage to meet the needs of poor populations. Copyright © 2015 Verguet et al. Open access article published under the terms of CC BY-NC-SA. Published by .. All rights reserved.

Community-Based Surveillance to Monitor Mortality in a Malaria-Endemic and Ebola-Epidemic Setting in Rural Guinea.

PubMed

Tiffany, Amanda; Moundekeno, Faya Pascal; Traoré, Alexis; Haile, Melat; Sterk, Esther; Guilavogui, Timothé; Serafini, Micaela; Genton, Blaise; Grais, Rebecca F

2016-12-07

Multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. Community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. We retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (Koundou) in Guinea. Deaths were recorded by key informants and classified as due to malaria or another cause. Malaria deaths were those reported as due to malaria or fever in the 3 days before death with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those due to select symptoms in the EVD case definition. Deaths were aggregated by sous-préfecture and analyzed by a 6-month period. A total of 43,000 individuals were monitored by the surveillance system; 1,242 deaths were reported from July 2011-June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria-attributable proportional mortality decreased by 26.5% (95% confidence interval [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3-30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were reported from November 2013 to March 2014 including the first two laboratory-confirmed EVD deaths. Community surveillance can capture information on mortality in areas where data collection is weak, but determining causes of death remains challenging. It can also be useful for outbreak detection if timeliness of data collection and reporting facilitate real-time data analysis. © The American Society of Tropical Medicine and Hygiene.

A qualitative study of attitudes and values surrounding stillbirth and neonatal mortality among grandmothers, mothers, and unmarried girls in rural Amhara and Oromiya regions, Ethiopia: unheard souls in the backyard.

PubMed

Sisay, Mitike Molla; Yirgu, Robel; Gobezayehu, Abebe Gebremariam; Sibley, Lynn M

2014-01-01

In Ethiopia, neonatal mortality and stillbirth are high and underreported. This study explored values related to neonatal mortality and stillbirth and the visibility of these deaths in rural Ethiopia among 3 generations of women. We conducted a qualitative study in 6 rural districts of the Oromiya and Amhara regional states during May 2012. We included 30 focus groups representing grandmothers, married women (mothers), and unmarried girls in randomly selected kebeles (villages). Until the 40th day of life, neonates are considered to be strangers to the community (not human). Their deaths are not talked about; they are buried in the house or in the backyard. Mothers are forbidden to mourn their loss lest they offend God and bring on future neonatal losses. Women who repeatedly lose their neonates may be blamed, mistreated, and dishonored through divorce. Neonatal death and stillbirth are attributed to supernatural powers, although some women and girls associate these deaths with poverty and lack of education. The desire for increased visibility of neonatal death is mixed. Unlike the grandmothers and unmarried girls, most of the married women want death to be visible to draw the attention of policy makers. Women prefer home birth and consider themselves lucky to be able to give birth at home. At present, there is no national vital registration system. Neonatal death and stillbirth are hidden and the magnitude is likely underrepresented. The delayed recognition of personhood, attribution of death to supernatural causes, social repercussions for women who experience a pregnancy loss, preference for home birth, and lack of a vital registration system all contribute to the invisibility of perinatal deaths. Increasing the visibility of (and counting) these deaths may require multifaceted behavior-change interventions. © 2014 by the American College of Nurse-Midwives.

Effect of cocaine on Fas-associated protein with death domain in the rat brain: individual differences in a model of differential vulnerability to drug abuse.

PubMed

García-Fuster, María-Julia; Clinton, Sarah M; Watson, Stanley J; Akil, Huda

2009-04-01

This study was designed to (1) assess the effects of cocaine on Fas-associated protein with death domain (FADD) system and its role in the activation of apoptotic vs nonapoptotic events and (2) ascertain whether animals selectively bred for their differential propensity to drug-seeking show differences in FADD levels or response to cocaine. Acute cocaine, through D(2) dopamine receptors, induced a dose-response increase in FADD protein in the cortex, with opposite effects over pFADD (Ser191/194), and no induction of apoptotic cell death (poly-(ADP-ribose) polymerase cleavage). FADD was increased by cocaine in cytosol (approximately 142%), membranes (approximately 23%) and nucleus (approximately 54%). The modulation of the FADD system showed tolerance of the acute effect over time, as well as a compensatory response on withdrawal that mirrored the acute effect--ie a transient FADD decrease on day 3 of withdrawal, both at mRNA and protein levels. In a second experiment, possible FADD differences were investigated in rats selectively bred for differential responsiveness to novelty, propensity for drug-seeking and cocaine sensitization. High-responders (HR), who were more prone to drug abuse, exhibited higher FADD and lower pFADD levels than low-responder (LR) rats. However, HR and LR rats showed similar rates of cocaine-induced apoptosis, and exhibited a parallel impact of cocaine over FADD within each phenotype. Thus, FADD is a signaling protein modulated by cocaine, regulating apoptosis/proliferative mechanisms in relation to its FADD/pFADD content. Interestingly, animals selectively bred for differential propensity to substance abuse show basal differences in the expression of this protein, suggesting FADD may also be a molecular correlate for the HR/LR phenotype.

Apoptosis evaluation in epithelial cells exposed to different chemicals: relevance of floating cells.

PubMed

Turco, L; De Angelis, I; Stammati, A; Zucco, F

2000-01-01

The recent increase in understanding of cell death has promoted new approaches in toxicological studies, mainly those dealing with in vitro systems where the evaluation of cell death has been the most widely adopted end-point in measuring the effects of chemical toxicants. The aim of this study was to investigate the possibility of improving the traditional cytotoxicity test protocols in order to produce more specific information on the type of cell death induced by exposure to toxicants. In particular, we characterized the mode of cell death in an established epithelial cell line, HEp-2 cells, which is frequently used in cytotoxicity testing owing to its easy handling and standardization of culture conditions. Reference chemicals for apoptosis and necrosis were selected as controls, together with other molecules that have been shown, in preliminary studies, to induce various morphological and structural modifications in relation to cell death. The results obtained show that: (a) the floating fraction of treated cells gives the clearest picture of the necrotic/apoptotic distribution; (b) morphological analysis is crucial for characterization of apoptosis; (c) more than one cytotoxic end-point is necessary to clearly identify the type of cell death.

Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination

PubMed Central

Linden, Jennifer R.; Ma, Yinghua; Zhao, Baohua; Harris, Jason Michael; Rumah, Kareem Rashid; Schaeren-Wiemers, Nicole

2015-01-01

ABSTRACT Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody. PMID:26081637

Associations and Trends in Cause-Specific Rates of Death Among Persons Reported with HIV Infection, 23 U.S. Jurisdictions, Through 2011.

PubMed

Adih, William K; Selik, Richard M; Hall, H Irene; Babu, Aruna Surendera; Song, Ruiguang

2016-01-01

Published death rates for persons with HIV have not distinguished deaths due to HIV from deaths due to other causes. Cause-specific death rates would allow better assessment of care needs. Using data reported to the US national HIV surveillance system, we examined a) associations between selected decedent characteristics and causes of death during 2007-2011, b) trends in rates of death due to underlying causes among persons with AIDS during 1990-2011, and among all persons with diagnosed HIV infection (with or without AIDS) during 2000-2011. During 2007-2011, non-HIV-attributable causes of death with the highest rates per 1,000 person-years were heart disease (2.0), non-AIDS cancers other than lung cancer (1.4), and accidents (0.8). During 1990-2011, among persons with AIDS, the annual rate of death due to HIV-attributable causes decreased by 89% (from 122.0 to 13.2), and the rate due to non-HIV-attributable-causes decreased by 57% (from 20.0 to 8.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 11% to 43%. During 2000-2011, among persons with HIV infection, the rate of death due to HIV-attributable causes decreased by 69% (from 26.4 to 8.3), and the rate due to non-HIV-attributable causes decreased by 28% (from 10.5 to 7.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 25% to 48%. Among HIV-infected persons, as rates of death due to HIV-attributable causes decreased, rates due to non-HIV-attributable causes also decreased, but the percentages of deaths due to non-HIV-attributable causes, such as heart disease and non-AIDS cancers increased.

Counting every stillbirth and neonatal death through mortality audit to improve quality of care for every pregnant woman and her baby

PubMed Central

2015-01-01

Background While there is widespread acknowledgment of the need for improved quality and quantity of information on births and deaths, there has been less movement towards systematically capturing and reviewing the causes and avoidable factors linked to deaths, in order to affect change. This is particularly true for stillbirths and neonatal deaths which can fall between different health care providers and departments. Maternal and perinatal mortality audit applies to two of the five objectives in the Every Newborn Action Plan but data on successful approaches to overcome bottlenecks to scaling up audit are lacking. Methods We reviewed the current evidence for facility-based perinatal mortality audit with a focus on low- and middle-income countries and assessed the status of mortality audit policy and implementation. Based on challenges identified in the literature, key challenges to completing the audit cycle and affecting change were identified across the WHO health system building blocks, along with solutions, in order to inform the process of scaling up this strategy with attention to quality. Results Maternal death surveillance and review is moving rapidly with many countries enacting and implementing policies and with accountability beyond the single facility conducting the audits. While 51 priority countries report having a policy on maternal death notification in 2014, only 17 countries have a policy for reporting and reviewing stillbirths and neonatal deaths. The existing evidence demonstrates the potential for audit to improve birth outcomes, only if the audit cycle is completed. The primary challenges within the health system building blocks are in the area of leadership and health information. Examples of successful implementation exist from high income countries and select low- and middle-income countries provide valuable learning, especially on the need for leadership for effective audit systems and on the development and the use of clear guidelines and protocols in order to ensure that the audit cycle is completed. Conclusions Health workers have the power to change health care routines in daily practice, but this must be accompanied by concrete inputs at every level of the health system. The system requires data systems including consistent cause of death classification and use of best practice guidelines to monitor performance, as well as leaders to champion the process, especially to ensure a no-blame environment, and to access change agents at other levels to address larger, systemic challenges. PMID:26391558

Density behavior of spatial birth-and-death stochastic evolution of mutating genotypes under selection rates

NASA Astrophysics Data System (ADS)

Finkelshtein, D.; Kondratiev, Yu.; Kutoviy, O.; Molchanov, S.; Zhizhina, E.

2014-10-01

We consider birth-and-death stochastic evolution of genotypes with different lengths. The genotypes might mutate, which provides a stochastic changing of lengths by a free diffusion law. The birth and death rates are length dependent, which corresponds to a selection effect. We study an asymptotic behavior of a density for an infinite collection of genotypes. The cases of space homogeneous and space heterogeneous densities are considered.

Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact.

PubMed

Belousov, Andrei B; Wang, Yongfu; Song, Ji-Hoon; Denisova, Janna V; Berman, Nancy E; Fontes, Joseph D

2012-08-22

In the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-Jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury. The results suggest that neuronal gap junctions play a critical role in the CCI-induced secondary neuronal death. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Black Holes: A Selected Bibliography.

ERIC Educational Resources Information Center

Fraknoi, Andrew

1991-01-01

Offers a selected bibliography pertaining to black holes with the following categories: introductory books; introductory articles; somewhat more advanced articles; readings about Einstein's general theory of relativity; books on the death of stars; articles on the death of stars; specific articles about Supernova 1987A; relevant science fiction…

Relation of Total and Cardiovascular Death Rates to Climate System, Temperature, Barometric Pressure, and Respiratory Infection.

PubMed

Schwartz, Bryan G; Qualls, Clifford; Kloner, Robert A; Laskey, Warren K

2015-10-15

A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there were 2,526,123 all-cause deaths, 838,264 circulatory deaths, 255,273 coronary heart disease deaths, and 135,801 ST-elevation myocardial infarction (STEMI) deaths. We used time series and multivariate regression modeling to explore the association between death rates and climatic factors (temperature, dew point, precipitation, barometric pressure), influenza levels, air pollution levels, hours of daylight, and day of week. Average seasonal patterns for all-cause and cardiovascular deaths were very similar across the 7 locations despite differences in climate. After adjusting for multiple covariates and potential confounders, there was a 0.49% increase in all-cause death rate for every 1°C decrease. In general, all-cause, circulatory, coronary heart disease and STEMI death rates increased linearly with decreasing temperatures. The temperature effect varied by location, including temperature's linear slope, cubic fit, positional shift on the temperature axis, and the presence of circulatory death increases in locally hot temperatures. The variable effect of temperature by location suggests that people acclimatize to local temperature cycles. All-cause and circulatory death rates also demonstrated sizable associations with influenza levels, dew point temperature, and barometric pressure. A greater understanding of how climate, temperature, and barometric pressure influence cardiovascular responses would enhance our understanding of circulatory and STEMI deaths. Copyright © 2015 Elsevier Inc. All rights reserved.

Causes of Death among Children Aged 5 to 14 Years Old from 2008 to 2013 in Kersa Health and Demographic Surveillance System (Kersa HDSS), Ethiopia.

PubMed

Dedefo, Melkamu; Zelalem, Desalew; Eskinder, Biniyam; Assefa, Nega; Ashenafi, Wondimye; Baraki, Negga; Damena Tesfatsion, Melake; Oljira, Lemessa; Haile, Ashenafi

2016-01-01

The global burden of mortality among children is still very huge though its trend has started declining following the improvements in the living standard. It presents serious challenges to the well-being of children in many African countries. Today, Sub-Saharan Africa alone accounts for about 50% of global child mortality. The overall objective of this study was to determine the magnitude and distribution of causes of death among children aged 5 to 14 year olds in the population of Kersa HDSS using verbal autopsy method for the period 2008 to 2013. Kersa Health and Demographic Surveillance System(Kersa HDSS) was established in September 2007. The center consists of 10 rural and 2 urban kebeles which were selected randomly from 38 kebeles in the district. Thus this study was conducted in Kersa HDSS and data was taken from Kersa HDSS database. The study population included all children aged 5 to 14 years registered during the period of 2008 to 2013 in Kersa HDSS using age specific VA questionnaires. Data were extracted from SPSS database and analyzed using STATA. A total of 229 deaths were recorded over the period of six years with a crude death rate of 219.6 per 100,000 population of this age group over the study period. This death rate was 217.5 and 221.5 per 100,000 populations for females and males, respectively. 75% of deaths took place at home. The study identified severe malnutrition(33.9%), intestinal infectious diseases(13.8%) and acute lower respiratory infections(9.2%) to be the three most leading causes of death. In broad causes of death classification, injuries have been found to be the second most cause of death next to communicable diseases(56.3%) attributing to 13.1% of the total deaths. In specific causes of death classification severe malnutrition, intestinal infectious diseases and acute lower respiratory infections were the three leading causes of death where, in broad causes of death communicable diseases and injuries were among the leading causes of death. Hence, concerned bodies should take measures to avert the situation of mortality from these causes of death and further inferential analysis into the prevention and management of infectious diseases should also be taken.

Lifetime competing risks between coronary heart disease mortality and other causes of death during 50years of follow-up.

PubMed

Puddu, Paolo Emilio; Piras, Paolo; Menotti, Alessandro

2017-02-01

To study coronary heart disease (CHD) death versus 11 other causes of death using the cumulative incidence function (CIF) and the competing risks procedures to disentangle the differential role of risk factors for different end-points. Standard Cox and Fine-Gray models among 1712 middle-aged men were compared during 50years of follow-up. CHD death was the primary event, while deaths from 11 selected causes, mutually exclusive from the primary end-point, were considered as secondary events. Reverse solutions were also performed. We considered 10 selected risk factors. CHD death risk was the second highest among 12 mostly specific causes of death. Some risk factors were specific: serum cholesterol for CHD death whereas, systolic blood pressure, cigarette smoking and age may have a differential role in other causes of death. Application of the Fine-Gray model based on CIF enabled to dissect, at least in part, the respective role that baseline covariates may have to segregate the probabilities of two types of death in contrast from each other. They also point to the absence of contributing significance for some of the selected risk factors and this calls for a parsimonious approach in predictions. The relative rarity of competing risk challenges when defining the risk factors role at long-term needs now be corrected since we have clearly shown, with Fine-Gray model, at direct or reverse use, that comparing different end-points heavily influences the risk factor predictive capacity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mapping dominant negative mutation for triforine sensitivity in lettuce and its use as a selectable marker for detecting hybrids.

USDA-ARS?s Scientific Manuscript database

Some lettuce cultivars are highly sensitive to triforine, an inhibitor of sterol biosynthesis found in some commercial systemic fungicides. First symptoms of a sensitive reaction are usually observed within 24 to 48 hours after treatment and include severe wilting, necrosis and rapid plant death. We...

Resources for Helping Young Children Deal with Death.

ERIC Educational Resources Information Center

Wass, Hannelore

This bibliography contains selected resources (1965-1983) to help parents and teachers assist young children with death-related concerns. Included are materials for adults: an annotated list of books on death (13 citations); a bibliography of articles about children and death from recent literature (50 citations); and an annotated list of…

42 CFR 110.82 - Calculation of death benefits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Calculation of death benefits. 110.82 Section 110... COUNTERMEASURES INJURY COMPENSATION PROGRAM Calculation and Payment of Benefits § 110.82 Calculation of death... file a written selection to receive death benefits under the alternative calculation, as described in...

42 CFR 110.82 - Calculation of death benefits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Calculation of death benefits. 110.82 Section 110... COUNTERMEASURES INJURY COMPENSATION PROGRAM Calculation and Payment of Benefits § 110.82 Calculation of death... file a written selection to receive death benefits under the alternative calculation, as described in...

42 CFR 110.82 - Calculation of death benefits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Calculation of death benefits. 110.82 Section 110... COUNTERMEASURES INJURY COMPENSATION PROGRAM Calculation and Payment of Benefits § 110.82 Calculation of death... file a written selection to receive death benefits under the alternative calculation, as described in...

42 CFR 110.82 - Calculation of death benefits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Calculation of death benefits. 110.82 Section 110... COUNTERMEASURES INJURY COMPENSATION PROGRAM Calculation and Payment of Benefits § 110.82 Calculation of death... file a written selection to receive death benefits under the alternative calculation, as described in...

Evolutionary games of condensates in coupled birth–death processes

PubMed Central

Knebel, Johannes; Weber, Markus F.; Krüger, Torben; Frey, Erwin

2015-01-01

Condensation phenomena arise through a collective behaviour of particles. They are observed in both classical and quantum systems, ranging from the formation of traffic jams in mass transport models to the macroscopic occupation of the energetic ground state in ultra-cold bosonic gases (Bose–Einstein condensation). Recently, it has been shown that a driven and dissipative system of bosons may form multiple condensates. Which states become the condensates has, however, remained elusive thus far. The dynamics of this condensation are described by coupled birth–death processes, which also occur in evolutionary game theory. Here we apply concepts from evolutionary game theory to explain the formation of multiple condensates in such driven-dissipative bosonic systems. We show that the vanishing of relative entropy production determines their selection. The condensation proceeds exponentially fast, but the system never comes to rest. Instead, the occupation numbers of condensates may oscillate, as we demonstrate for a rock–paper–scissors game of condensates. PMID:25908384

Early Invasive Versus Selective Strategy for Non-ST-Segment Elevation Acute Coronary Syndrome: The ICTUS Trial.

PubMed

Hoedemaker, Niels P G; Damman, Peter; Woudstra, Pier; Hirsch, Alexander; Windhausen, Fons; Tijssen, Jan G P; de Winter, Robbert J

2017-04-18

The ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes) trial compared early invasive strategy with a selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and an elevated cardiac troponin T. No long-term benefit of an early invasive strategy was found at 1 and 5 years. The aim of this study was to determine the 10-year clinical outcomes of an early invasive strategy versus a selective invasive strategy in patients with NSTE-ACS and an elevated cardiac troponin T. The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization. Ten-year death or spontaneous MI was not statistically different between the 2 groups (33.8% vs. 29.0%, hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 0.97 to 1.46; p = 0.11). Revascularization occurred in 82.6% of the early invasive group and 60.5% in the selective invasive group. There were no differences in additional outcomes, except for a higher rate of death or MI in the early invasive group compared with the rates for the selective invasive group (37.6% vs. 30.5%; HR: 1.30; 95% CI: 1.07 to 1.58; p = 0.009), driven by a higher rate of procedure-related MI in the early invasive group (6.5% vs. 2.4%; HR: 2.82; 95% CI: 1.53 to 5.20; p = 0.001). In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China

PubMed Central

Wang, Ziqian; Wang, Yanhong; Zhu, Rongrong; Tian, Xinping; Xu, Dong; Wang, Qian; Wu, Chanyuan; Zhang, Shangzhu; Zhao, Jiuliang; Zhao, Yan; Li, Mengtao; Zeng, Xiaofeng

2015-01-01

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China. This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China. The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China. We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China. The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators. All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the top 4 causes. The overall survival rates for Chinese patients with SLE resembled previous publications in Asia-Pacific area. But the death causes of SLE in China were of some differences indicating relatively higher proportion of infection and lupus encephalopathy and lower cardiovascular disease. Ethnicity and more aggressive treatment might have contributed to the difference in death composition. PMID:25929930

Impact of brain death on ischemia/reperfusion injury in liver transplantation.

PubMed

Dziodzio, Tomasz; Biebl, Matthias; Pratschke, Johann

2014-04-01

In liver transplantation, the ischemia/reperfusion injury (IRI) is influenced by factors related to graft quality, organ procurement and the transplant procedure itself. However, in brain-dead donors, the process of death itself also thoroughly affects organ damage through breakdown of the autonomous nervous system and subsequent massive cytokine release. This review highlights the actual knowledge on these proinflammatory effects of brain death on IRI in liver transplantation. Brain death affects IRI either through hemodynamical or molecular effects with proinflammatory activation. Immunological effects are mainly mediated through Kupffer cell activation, leading to TNF-α and TLR4 amplification. Proinflammatory cytokines such as interleukin (IL)-6, IL-10, TNF-β and MIP-1α are released, together with activation of the innate immune system via natural killer cells and natural killer T cells, which promote organ damage and activation of fibrosis. Preprocurement treatment regimens attempt to hamper inflammatory response by the application of methylprednisolone or thymoglobulin to the donor. Selective P-selectin antagonism resulted in improved function in marginal liver grafts. Inhaled nitric oxide was found to reduce apoptosis in liver grafts. Other medications like the immunosuppressant tacrolimus produced conflicting results regarding organ protection. Furthermore, improved organ storage after procurement - such as machine perfusion - can diminish effects of IRI in a clinical setting. Brain death plays a fundamental role in the regulation of molecular markers triggering inflammation and IRI-related tissue damage in liver transplants. Although several treatment options have reached clinical application, to date, the effects of brain death during donor conditioning and organ procurement remain relevant for organ function and survival.

IN VITRO RESEARCH OF THE ALTERATION OF NEURONS IN VAGAL CORE IN MEDULLA OBLONGATA AT ASPHYXIC DEATHS

PubMed Central

Haliti, Naim; Islami, Hilmi; Elezi, Nevzat; Shabani, Ragip; Abdullahu, Bedri; Dragusha, Gani

2010-01-01

The aim of this study was to research the morphological changes of neurons in the vagus nerve nuclei in medulla oblongata in asphyxia related death cases. Morphological changes that were investigated were mainly in the dorsal motor respiratory center (DMRC), nucleus tractus solitarius (nTS) and nucleus ambigus (nA) in the medulla oblongata. In our research, the autopsy material from asphyxia related death cases was used from various etiologies: monoxide carbon (CO), liquid drowning, strangulation, electricity, clinical-pathological death, firing weapon, explosive weapon, sharp and blunt objects and death cases due to accident. The material selected for research was taken from medulla oblongata and lungs from all lobes. The material from the medulla oblongata and lungs was fixed in a 10% solution of buffered formalin. Special histochemical methods for central nervous system (CNS) were employed like: Cresyl echt violet, toluidin blue, Sevier-Munger modification and Grimelius. For stereometrical analysis of the quantitative density of the neurons the universal testing system Weibel M42 was used. The acquired results show that in sudden asphyxia related death cases, there are alterations in the nuclei of vagal nerve in form of: central chromatolysis, axonal retraction, axonal fragmentation, intranuclear vacuolization, cytoplasmic vacuolization, edema, condensation and dispersion of substance of Nissl, proliferation of oligodendrocytes, astrocytes and microglia. The altered population of vagus nerve neurons does not show an important statistica! significarne compared to the overall quantity of the neurons in the nuclei of the vagus nerve (p<0,05). PMID:20846134

Most Undirected Random Graphs Are Amplifiers of Selection for Birth-Death Dynamics, but Suppressors of Selection for Death-Birth Dynamics.

PubMed

Hindersin, Laura; Traulsen, Arne

2015-11-01

We analyze evolutionary dynamics on graphs, where the nodes represent individuals of a population. The links of a node describe which other individuals can be displaced by the offspring of the individual on that node. Amplifiers of selection are graphs for which the fixation probability is increased for advantageous mutants and decreased for disadvantageous mutants. A few examples of such amplifiers have been developed, but so far it is unclear how many such structures exist and how to construct them. Here, we show that almost any undirected random graph is an amplifier of selection for Birth-death updating, where an individual is selected to reproduce with probability proportional to its fitness and one of its neighbors is replaced by that offspring at random. If we instead focus on death-Birth updating, in which a random individual is removed and its neighbors compete for the empty spot, then the same ensemble of graphs consists of almost only suppressors of selection for which the fixation probability is decreased for advantageous mutants and increased for disadvantageous mutants. Thus, the impact of population structure on evolutionary dynamics is a subtle issue that will depend on seemingly minor details of the underlying evolutionary process.

Systematic review of statistics on causes of deaths in hospitals: strengthening the evidence for policy-makers.

PubMed

Rampatige, Rasika; Mikkelsen, Lene; Hernandez, Bernardo; Riley, Ian; Lopez, Alan D

2014-11-01

To systematically review the reliability of hospital data on cause of death and encourage periodic reviews of these data using a standard method. We searched Google Scholar, Pubmed and Biblioteca Virtual de la Salud for articles in English, Spanish and Portuguese that reported validation studies of data on cause of death. We analysed the results of 199 studies that had used medical record reviews to validate the cause of death reported on death certificates or by the vital registration system. The screened studies had been published between 1983 and 2013 and their results had been reported in English (n = 124), Portuguese (n = 25) or Spanish (n = 50). Only 29 of the studies met our inclusion criteria. Of these, 13 had examined cause of death patterns at the population level - with a view to correcting cause-specific mortality fractions - while the other 16 had been undertaken to identify discrepancies in the diagnosis for specific diseases before and after medical record review. Most of the selected studies reported substantial misdiagnosis of causes of death in hospitals. There was wide variation in study methodologies. Many studies did not describe the methods used in sufficient detail to be able to assess the reproducibility or comparability of their results. The assumption that causes of death are being accurately reported in hospitals is unfounded. To improve the reliability and usefulness of reported causes of death, national governments should do periodic medical record reviews to validate the quality of their hospital cause of death data, using a standard.

Systematic review of statistics on causes of deaths in hospitals: strengthening the evidence for policy-makers

PubMed Central

Rampatige, Rasika; Mikkelsen, Lene; Hernandez, Bernardo; Riley, Ian

2014-01-01

Abstract Objective To systematically review the reliability of hospital data on cause of death and encourage periodic reviews of these data using a standard method. Methods We searched Google Scholar, Pubmed and Biblioteca Virtual de la Salud for articles in English, Spanish and Portuguese that reported validation studies of data on cause of death. We analysed the results of 199 studies that had used medical record reviews to validate the cause of death reported on death certificates or by the vital registration system. Findings The screened studies had been published between 1983 and 2013 and their results had been reported in English (n = 124), Portuguese (n = 25) or Spanish (n = 50). Only 29 of the studies met our inclusion criteria. Of these, 13 had examined cause of death patterns at the population level – with a view to correcting cause-specific mortality fractions – while the other 16 had been undertaken to identify discrepancies in the diagnosis for specific diseases before and after medical record review. Most of the selected studies reported substantial misdiagnosis of causes of death in hospitals. There was wide variation in study methodologies. Many studies did not describe the methods used in sufficient detail to be able to assess the reproducibility or comparability of their results. Conclusion The assumption that causes of death are being accurately reported in hospitals is unfounded. To improve the reliability and usefulness of reported causes of death, national governments should do periodic medical record reviews to validate the quality of their hospital cause of death data, using a standard. PMID:25378742

Using community-based reporting of vital events to monitor child mortality: Lessons from rural Ghana.

PubMed

Helleringer, Stephane; Arhinful, Daniel; Abuaku, Benjamin; Humes, Michael; Wilson, Emily; Marsh, Andrew; Clermont, Adrienne; Black, Robert E; Bryce, Jennifer; Amouzou, Agbessi

2018-01-01

Reducing neonatal and child mortality is a key component of the health-related sustainable development goal (SDG), but most low and middle income countries lack data to monitor child mortality on an annual basis. We tested a mortality monitoring system based on the continuous recording of pregnancies, births and deaths by trained community-based volunteers (CBV). This project was implemented in 96 clusters located in three districts of the Northern Region of Ghana. Community-based volunteers (CBVs) were selected from these clusters and were trained in recording all pregnancies, births, and deaths among children under 5 in their catchment areas. Data collection lasted from January 2012 through September 2013. All CBVs transmitted tallies of recorded births and deaths to the Ghana Birth and deaths registry each month, except in one of the study districts (approximately 80% reporting). Some events were reported only several months after they had occurred. We assessed the completeness and accuracy of CBV data by comparing them to retrospective full pregnancy histories (FPH) collected during a census of the same clusters conducted in October-December 2013. We conducted all analyses separately by district, as well as for the combined sample of all districts. During the 21-month implementation period, the CBVs reported a total of 2,819 births and 137 under-five deaths. Among the latter, there were 84 infant deaths (55 neonatal deaths and 29 post-neonatal deaths). Comparison of the CBV data with FPH data suggested that CBVs significantly under-estimated child mortality: the estimated under-5 mortality rate according to CBV data was only 2/3 of the rate estimated from FPH data (95% Confidence Interval for the ratio of the two rates = 51.7 to 81.4). The discrepancies between the CBV and FPH estimates of infant and neonatal mortality were more limited, but varied significantly across districts. In northern Ghana, a community-based data collection systems relying on volunteers did not yield accurate estimates of child mortality rates. Additional implementation research is needed to improve the timeliness, completeness and accuracy of such systems. Enhancing pregnancy monitoring, in particular, may be an essential step to improve the measurement of neonatal mortality.

Water-level database update for the Death Valley regional groundwater flow system, Nevada and California, 1907-2007

USGS Publications Warehouse

Pavelko, Michael T.

2010-01-01

The water-level database for the Death Valley regional groundwater flow system in Nevada and California was updated. The database includes more than 54,000 water levels collected from 1907 to 2007, from more than 1,800 wells. Water levels were assigned a primary flag and multiple secondary flags that describe hydrologic conditions and trends at the time of the measurement and identify pertinent information about the well or water-level measurement. The flags provide a subjective measure of the relative accuracy of the measurements and are used to identify which water levels are appropriate for calculating head observations in a regional transient groundwater flow model. Included in the report appendix are all water-level data and their flags, selected well data, and an interactive spreadsheet for viewing hydrographs and well locations.

Lavia – an Evaluation of the Potential Safety Benefits of the French Intelligent Speed Adaptation Project

PubMed Central

Driscoll, R.; Page, Y.; Lassarre, S.; Ehrlich, J.

2007-01-01

This paper presents the potential safety benefits of the experimental French LAVIA Intelligent Speed Adaptation system, according to road network and system mode, based on observed driving speeds, distributions of crash severity and crash injury risk. Results are given for car frontal and side impacts that together, represent 80% of all serious and fatal injuries in France. Of the three system modes tested (advisory, driver select, mandatory), our results suggest that driver select would most significantly reduce serious injuries and death. We estimate this 100% utilization of cars equipped with this type of speed adaptation system would decrease injury rates by 6% to 16% over existing conditions depending on the type of crash (frontal or side) and road environment considered. Some limitations associated with the analysis are also identified. PMID:18184509

Dying for work: The magnitude of US mortality from selected causes of death associated with occupation.

PubMed

Steenland, Kyle; Burnett, Carol; Lalich, Nina; Ward, Elizabeth; Hurrell, Joseph

2003-05-01

Deaths due to occupational disease and injury place a heavy burden on society in terms of economic costs and human suffering. We estimate the annual deaths due to selected diseases for which an occupational association is reasonably well established and quantifiable, by calculation of attributable fractions (AFs), with full documentation; the deaths due to occupational injury are then added to derive an estimated number of annual deaths due to occupation. Using 1997 US mortality data, the estimated annual burden of occupational disease mortality resulting from selected respiratory diseases, cancers, cardiovascular disease, chronic renal failure, and hepatitis is 49,000, with a range from 26,000 to 72,000. The Bureau of Labor Statistics estimates there are about 6,200 work-related injury deaths annually. Adding disease and injury data, we estimate that there are a total of 55,200 US deaths annually resulting from occupational disease or injury (range 32,200-78,200). Our estimate is in the range reported by previous investigators, although we have restricted ourselves more than others to only those diseases with well-established occupational etiology, biasing our estimates conservatively. The underlying assumptions and data used to generate the estimates are well documented, so our estimates may be updated as new data emerges on occupational risks and exposed populations, providing an advantage over previous studies. We estimate that occupational deaths are the 8th leading cause of death in the US, after diabetes (64,751) but ahead of suicide (30,575), and greater than the annual number of motor vehicle deaths per year (43,501). Copyright 2003 Wiley-Liss, Inc.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths

PubMed Central

Sorg, Marcella H.; Long, D. Leann; Abate, Marie A.; Kaplan, James A.; Kraner, James C.; Greenwald, Margaret S.; Andrew, Thomas A.; Shapiro, Steven L.; Wren, Jamie A.

2017-01-01

A forensic drug database (FDD) was used to capture comprehensive data from all drug-related deaths in West Virginia, with deaths also included from the northern New England states of Maine, Vermont, and New Hampshire. All four states serve predominantly rural populations under two million and all have similar state medical examiner systems that employ statewide uniform death certification policies and practices. This study focused on 1482 single opioid deaths (fentanyl, hydrocodone, methadone, and oxycodone) in the FDD from 2007–2011. We modeled relationships between the opioid concentrations and the presence or absence of the following commonly occurring non-opioid cointoxicants: benzodiazepines (alprazolam and diazepam), alcohol, tricyclic antidepressants, selective serotonin reuptake inhibitors, and diphenhydramine. Additional covariates of state, age, body mass index, and sex were included. Results showed that the presence of alcohol, benzodiazepines, and antidepressants were each associated with statistically significant lower concentrations of some but not all of the opioids studied, which may obscure the interpretation of postmortem toxicology results alone. Fentanyl concentrations appeared to be the least associated with the presence or absence of the variables studied, and cointoxicant alcohol appeared to be associated with lower concentrations in opioid concentrations than were most of the other factors in the model studied. These findings underscore the importance of documenting all potential cointoxicants in opioid-related deaths. PMID:29399239

The Enemy within: Innate Surveillance-Mediated Cell Death, the Common Mechanism of Neurodegenerative Disease

PubMed Central

Richards, Robert I.; Robertson, Sarah A.; O'Keefe, Louise V.; Fornarino, Dani; Scott, Andrew; Lardelli, Michael; Baune, Bernhard T.

2016-01-01

Neurodegenerative diseases comprise an array of progressive neurological disorders all characterized by the selective death of neurons in the central nervous system. Although, rare (familial) and common (sporadic) forms can occur for the same disease, it is unclear whether this reflects several distinct pathogenic pathways or the convergence of different causes into a common form of nerve cell death. Remarkably, neurodegenerative diseases are increasingly found to be accompanied by activation of the innate immune surveillance system normally associated with pathogen recognition and response. Innate surveillance is the cell's quality control system for the purpose of detecting such danger signals and responding in an appropriate manner. Innate surveillance is an “intelligent system,” in that the manner of response is relevant to the magnitude and duration of the threat. If possible, the threat is dealt with within the cell in which it is detected, by degrading the danger signal(s) and restoring homeostasis. If this is not successful then an inflammatory response is instigated that is aimed at restricting the spread of the threat by elevating degradative pathways, sensitizing neighboring cells, and recruiting specialized cell types to the site. If the danger signal persists, then the ultimate response can include not only the programmed cell death of the original cell, but the contents of this dead cell can also bring about the death of adjacent sensitized cells. These responses are clearly aimed at destroying the ability of the detected pathogen to propagate and spread. Innate surveillance comprises intracellular, extracellular, non-cell autonomous and systemic processes. Recent studies have revealed how multiple steps in these processes involve proteins that, through their mutation, have been linked to many familial forms of neurodegenerative disease. This suggests that individuals harboring these mutations may have an amplified response to innate-mediated damage in neural tissues, and renders innate surveillance mediated cell death a plausible common pathogenic pathway responsible for neurodegenerative diseases, in both familial and sporadic forms. Here we have assembled evidence in favor of the hypothesis that neurodegenerative disease is the cumulative result of chronic activation of the innate surveillance pathway, triggered by endogenous or environmental danger or damage associated molecular patterns in a progressively expanding cascade of inflammation, tissue damage and cell death. PMID:27242399

Cancer selection.

PubMed

Leroi, Armand M; Koufopanou, Vassiliki; Burt, Austin

2003-03-01

Cancers are often thought to be selectively neutral. This is because most of the individuals that they kill are post-reproductive. Some cancers, however, kill the young and so select for anticancer adaptations that reduce the chance of death. These adaptations could reduce the somatic mutation rate or the selective value of a mutant clone of cells, or increase the number of stages required for neoplasia. New theory predicts that cancer selection--selection to prevent or postpone deaths due to cancer--should be especially important as animals evolve new morphologies or larger, longer-lived bodies, and might account for some of the differences in the causes of cancer between mice and men.

Youth Risk Behavior Surveillance System: Selected 2011 National Health Risk Behaviors and Health Outcomes by Sex

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2011

2011-01-01

The national Youth Risk Behavior Survey (YRBS) monitors priority health risk behaviors that contribute to the leading causes of death, disability, and social problems among youth and adults in the United States. The national YRBS is conducted every two years during the spring semester and provides data representative of 9th through 12th grade…

Thiol-redox signaling, dopaminergic cell death, and Parkinson's disease.

PubMed

Garcia-Garcia, Aracely; Zavala-Flores, Laura; Rodriguez-Rocha, Humberto; Franco, Rodrigo

2012-12-15

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta, which has been widely associated with oxidative stress. However, the mechanisms by which redox signaling regulates cell death progression remain elusive. Early studies demonstrated that depletion of glutathione (GSH), the most abundant low-molecular-weight thiol and major antioxidant defense in cells, is one of the earliest biochemical events associated with PD, prompting researchers to determine the role of oxidative stress in dopaminergic cell death. Since then, the concept of oxidative stress has evolved into redox signaling, and its complexity is highlighted by the discovery of a variety of thiol-based redox-dependent processes regulating not only oxidative damage, but also the activation of a myriad of signaling/enzymatic mechanisms. GSH and GSH-based antioxidant systems are important regulators of neurodegeneration associated with PD. In addition, thiol-based redox systems, such as peroxiredoxins, thioredoxins, metallothioneins, methionine sulfoxide reductases, transcription factors, as well as oxidative modifications in protein thiols (cysteines), including cysteine hydroxylation, glutathionylation, and nitrosylation, have been demonstrated to regulate dopaminergic cell loss. In this review, we summarize major advances in the understanding of the role of thiol-redox signaling in dopaminergic cell death in experimental PD. Future research is still required to clearly understand how integrated thiol-redox signaling regulates the activation of the cell death machinery, and the knowledge generated should open new avenues for the design of novel therapeutic approaches against PD.

The inducers of immunogenic cell death for tumor immunotherapy.

PubMed

Li, Xiuying

2018-01-01

Immunotherapy is a promising treatment modality that acts by selectively harnessing the host immune defenses against cancer. An effective immune response is often needed to eliminate tumors following treatment which can trigger the immunogenicity of dying tumor cells. Some treatment modalities (such as photodynamic therapy, high hydrostatic pressure or radiotherapy) and agents (some chemotherapeutic agents, oncolytic viruses) have been used to endow tumor cells with immunogenicity and/or increase their immunogenicity. These treatments and agents can boost the antitumor capacity by inducing immune responses against tumor neoantigens. Immunogenic cell death is a manner of cell death that can induce the emission of immunogenic damage-associated molecular patterns (DAMPs). DAMPs are sufficient for immunocompetent hosts to trigger the immune system. This review focuses on the latest developments in the treatment modalities and agents that can induce and/or enhance the immunogenicity of cancer cells.

Constitutive Activation of PINK1 Protein Leads to Proteasome-mediated and Non-apoptotic Cell Death Independently of Mitochondrial Autophagy*

PubMed Central

Akabane, Shiori; Matsuzaki, Kohei; Yamashita, Shun-ichi; Arai, Kana; Okatsu, Kei; Kanki, Tomotake; Matsuda, Noriyuki; Oka, Toshihiko

2016-01-01

Phosphatase and tensin homolog-induced putative kinase 1 (PINK1), a Ser/Thr kinase, and PARKIN, a ubiquitin ligase, are causal genes for autosomal recessive early-onset parkinsonism. Multiple lines of evidence indicate that PINK1 and PARKIN cooperatively control the quality of the mitochondrial population via selective degradation of damaged mitochondria by autophagy. Here, we report that PINK1 and PARKIN induce cell death with a 12-h delay after mitochondrial depolarization, which differs from the time profile of selective autophagy of mitochondria. This type of cell death exhibited definite morphologic features such as plasma membrane rupture, was insensitive to a pan-caspase inhibitor, and did not involve mitochondrial permeability transition. Expression of a constitutively active form of PINK1 caused cell death in the presence of a pan-caspase inhibitor, irrespective of the mitochondrial membrane potential. PINK1-mediated cell death depended on the activities of PARKIN and proteasomes, but it was not affected by disruption of the genes required for autophagy. Furthermore, fluorescence and electron microscopic analyses revealed that mitochondria were still retained in the dead cells, indicating that PINK1-mediated cell death is not caused by mitochondrial loss. Our findings suggest that PINK1 and PARKIN play critical roles in selective cell death in which damaged mitochondria are retained, independent of mitochondrial autophagy. PMID:27302064

Mutation in Fas Ligand Impairs Maturation of Thymocytes Bearing Moderate Affinity T Cell Receptors

PubMed Central

Boursalian, Tamar E.; Fink, Pamela J.

2003-01-01

Fas ligand, best known as a death-inducer, is also a costimulatory molecule required for maximal proliferation of mature antigen-specific CD4+ and CD8+ T cells. We now extend the role of Fas ligand by showing that it can also influence thymocyte development. T cell maturation in some, but not all, strains of TCR transgenic mice is severely impaired in thymocytes expressing mutant Fas ligand incapable of interacting with Fas. Mutant Fas ligand inhibits neither negative selection nor death by neglect. Instead, it appears to modulate positive selection of thymocytes expressing both class I– and class II–restricted T cell receptors of moderate affinity for their positively selecting ligands. Fas ligand is therefore an inducer of death, a costimulator of peripheral T cell activation, and an accessory molecule in positive selection. PMID:12860933

[Maternal deaths related to social vulnerabilities. Results from the French confidential enquiry into maternal deaths, 2010-2012].

PubMed

Tessier, V; Leroux, S; Guseva-Canu, I

2017-12-01

The theme of deprivation is new for the ENCMM. In view of the perceived increase in the number of maternal deaths that may be related to a deprivation situation, we sought to understand the main dimensions that could contribute to maternal death in this context, in order to propose a definition. The selection of cases made a posteriori is mainly based on a qualitative judgment. Between 2010 and 2012, among the deaths evaluated by the CNEMM, one or more elements related to social vulnerability were identified in 8.6% of the cases (18 deaths). The direct criteria used were the concepts of "deprivation" or "social difficulties", difficulties of housing, language barriers and isolation. The absence of prenatal care was retained as an indirect marker. We excluded cases where psychiatric pathology and/or addiction were predominant. Of the 18 cases identified with deprivation factors, death was considered "unavoidable" in 2 cases (11%), "certainly avoidable" or "possibly avoidable" in 13 cases (72%). In 3 cases (17%), avoidability could not be determined. Avoidability was related to the content and adequacy of care in 11 cases out of 13 (85%) and the patient's interaction with the health care system in 10 of 18 cases (56%). The analysis of maternal deaths among women in precarious situations points out that the link between socio-economic deprivation and poor maternal health outcomes potentially includes a specific risk of maternal death. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Associations and Trends in Cause-Specific Rates of Death Among Persons Reported with HIV Infection, 23 U.S. Jurisdictions, Through 2011

PubMed Central

Adih, William K.; Selik, Richard M.; Hall, H. Irene; Babu, Aruna Surendera; Song, Ruiguang

2016-01-01

Background: Published death rates for persons with HIV have not distinguished deaths due to HIV from deaths due to other causes. Cause-specific death rates would allow better assessment of care needs. Methods: Using data reported to the US national HIV surveillance system, we examined a) associations between selected decedent characteristics and causes of death during 2007-2011, b) trends in rates of death due to underlying causes among persons with AIDS during 1990-2011, and among all persons with diagnosed HIV infection (with or without AIDS) during 2000-2011. Results: During 2007-2011, non-HIV-attributable causes of death with the highest rates per 1,000 person-years were heart disease (2.0), non-AIDS cancers other than lung cancer (1.4), and accidents (0.8). During 1990-2011, among persons with AIDS, the annual rate of death due to HIV-attributable causes decreased by 89% (from 122.0 to 13.2), and the rate due to non-HIV-attributable-causes decreased by 57% (from 20.0 to 8.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 11% to 43%. During 2000-2011, among persons with HIV infection, the rate of death due to HIV-attributable causes decreased by 69% (from 26.4 to 8.3), and the rate due to non-HIV-attributable causes decreased by 28% (from 10.5 to 7.6), while the percentage of deaths caused by non-HIV-attributable causes increased from 25% to 48%. Conclusion: Among HIV-infected persons, as rates of death due to HIV-attributable causes decreased, rates due to non-HIV-attributable causes also decreased, but the percentages of deaths due to non-HIV-attributable causes, such as heart disease and non-AIDS cancers increased. PMID:27708746

Risk factors for death in patients with severe asthma*

PubMed Central

Fernandes, Andréia Guedes Oliva; Souza-Machado, Carolina; Coelho, Renata Conceição Pereira; Franco, Priscila Abreu; Esquivel, Renata Miranda; Souza-Machado, Adelmir; Cruz, Álvaro Augusto

2014-01-01

OBJECTIVE: To identify risk factors for death among patients with severe asthma. METHODS: This was a nested case-control study. Among the patients with severe asthma treated between December of 2002 and December of 2010 at the Central Referral Outpatient Clinic of the Bahia State Asthma Control Program, in the city of Salvador, Brazil, we selected all those who died, as well as selecting other patients with severe asthma to be used as controls (at a ratio of 1:4). Data were collected from the medical charts of the patients, home visit reports, and death certificates. RESULTS: We selected 58 cases of deaths and 232 control cases. Most of the deaths were attributed to respiratory causes and occurred within a health care facility. Advanced age, unemployment, rhinitis, symptoms of gastroesophageal reflux disease, long-standing asthma, and persistent airflow obstruction were common features in both groups. Multivariate analysis showed that male gender, FEV1 pre-bronchodilator < 60% of predicted, and the lack of control of asthma symptoms were significantly and independently associated with mortality in this sample of patients with severe asthma. CONCLUSIONS: In this cohort of outpatients with severe asthma, the deaths occurred predominantly due to respiratory causes and within a health care facility. Lack of asthma control and male gender were risk factors for mortality. PMID:25210958

Impact of Selected Socio-demographic Factors on the Development of Mortality due to Circulatory System Diseases in the Slovak Republic.

PubMed

Gavurová, Beáta; Kubák, Matúš

2017-12-01

We mapped the situation within a group of diseases of the circulatory system (I00-I99) in the Slovak Republic during 1996-2014. We focused mainly on spatiotemporal differences in mortality while controlling for age and sex. We performed binary logistic regression aiming to reveal socio-demographic factors that influence the odds of dying due to diseases of the circulatory system (I00-I99). In our analysis, the dependent variable was death diagnosis and the independent variables were age, region, gender, and marital status. Our findings suggest that odds of dying due to diseases of the circulatory system (I00-I99) increased for every year of age by 5.4%. Within the period from 1996 to 2014, the risk of dying from diseases of the circulatory system decreased by 2% every year. We also documented the fact that being female raised the odds of dying due to diseases of the circulatory system (I00-I99) by 12.9% compared to males. Furthermore, it could be argued that serious differences in terms of regional distribution of deaths caused by diseases of the circulatory system (I00-I99) exist in the Slovak Republic. We present the development of diseases of the circulatory system (I00-I99) in the Slovak Republic. Differences in spatial distribution of deaths are documented as well as related gender differences. Our study can serve as a tool for policy makers and benchmark for professionals. Copyright© by the National Institute of Public Health, Prague 2017.

Questioning care at the end of life.

PubMed

Ruopp, Patricia; Good, Mary-Jo Delvecchio; Lakoma, Matthew; Gadmer, Nina M; Arnold, Robert M; Block, Susan D

2005-06-01

The goal of the larger study was to explore physicians' emotional responses to the death of their patients; this study analyzed a subset of physician transcripts to elucidate the construct of questioning care, which emerged from the larger study. To analyzes how physicians question care-expressing concern, unease, or uncertainty about treatment decisions and practices, errors, or adverse events-as they attend dying patients. Retrospective interview study of physicians caring for randomly selected deaths on the medical service of a major academic teaching hospital, using qualitative and quantitative measures. SETTING, SUBJECTS: 188 attendings, residents, and interns on the internal medical services of two academic medical centers were part of the larger study. A subsample of 75 physician narratives was selected for qualitative data analysis for this study. Qualitative measures included open-ended questions eliciting physicians' stories of the most recent and a most emotionally powerful patient death they have experienced. Grounded theory was used to analyze physician narratives. Quantitative instruments measured physician attitudes toward end-of-life care and responses to the most recent and most emotional patient death. Physicians question care more frequently in most emotional deaths (42%) than in most recent deaths (34%). Physicians question communication with patients and families and within medical teams, medical judgment and technique, standards of practice, and high-risk treatments, often assigning responsibility for medical management they perceive as inappropriate, futile, overly aggressive, or mistakes in judgment and technique. Responsibility ranges from the distal (the culture of medicine) to the proximal (personal). Frustration, guilt, and anger are more frequently expressed in these narratives when care is questioned. A typology of questioning care emerged from these physicians' narratives that parallels and reflects recent and classic research on medical error and the culture of medicine. Physicians' questions about care can contribute to designing training experiences for residents and to improving the quality of systems that affect patients' experiences at life's end and physicians' experiences in caring for dying patients.

Leading Causes of Cancer Mortality - Caribbean Region, 2003-2013.

PubMed

Razzaghi, Hilda; Quesnel-Crooks, Sarah; Sherman, Recinda; Joseph, Rachael; Kohler, Betsy; Andall-Brereton, Glennis; Ivey, Marsha A; Edwards, Brenda K; Mery, Les; Gawryszewski, Vilma; Saraiya, Mona

2016-12-16

Cancer is one of the leading causes of deaths worldwide (1); in 2012, an estimated 65% of all cancer deaths occurred in the less developed regions of the world (2). In the Caribbean region, cancer is the second leading cause of mortality, with an estimated 87,430 cancer-related deaths reported in 2012 (3). The Pan American Health Organization defines the Caribbean region as a group of 27 countries that vary in size, geography, resources, and surveillance systems.* CDC calculated site- and sex-specific proportions of cancer deaths and age-standardized mortality rates (ASMR) for 21 English- and Dutch-speaking Caribbean countries, the United States, and two U.S. territories (Puerto Rico and the U.S. Virgin Islands [USVI]), using the most recent 5 years of mortality data available from each jurisdiction during 2003-2013. The selection of years varied by availability of the data from the countries and territories in 2015. ASMR for all cancers combined ranged from 46.1 to 139.3 per 100,000. Among males, prostate cancers were the leading cause of cancer deaths, followed by lung cancers; the percentage of cancer deaths attributable to prostate cancer ranged from 18.4% in Suriname to 47.4% in Dominica, and the percentage of cancer deaths attributable to lung cancer ranged from 5.6% in Barbados to 24.4% in Bermuda. Among females, breast cancer was the most common cause of cancer deaths, ranging from 14.0% of cancer deaths in Belize to 29.7% in the Cayman Islands, followed by cervical cancer. Several of the leading causes of cancer deaths in the Caribbean can be reduced through primary and secondary preventions, including prevention of exposure to risk factors, screening, early detection, and timely and effective treatment.

Faith and End of Life in Nursing Homes

PubMed Central

Rubinstein, Robert L.; Black, Helen K.; Doyle, Patrick J.; Moss, Miriam; Moss, Sidney Z.

2011-01-01

This paper explores the role of religious belief in the experiences of dying and death in a Catholic nursing home. The home appeals to residents and their families due to the active religious presence. Thus, religion is a salient element of the “local culture” which exists in this long-term care setting. The preeminence of faith within the organization and the personal religious convictions of staff, residents, and families may drive how death and dying are discussed and experienced in this setting, as well as the meanings that are attached to them. This paper examines the relationship between faith and the experience and meaning of death in this nursing home. We present themes that emerged from open-ended interviews with residents, family members, and staff, gathered between 1996 and 2004. The data indicate that people select the home due to their Catholic faith and the home's religious tone. Themes also show that belief in God and an afterlife helps shape the experience of dying and death for our informants. Our paper does not compare ease of dying with other nursing homes or within other belief systems. PMID:21629755

Assessing the Quality of Death and Dying in an Integrated Health Care System in Rural Pennsylvania.

PubMed

Darer, Jonathan D; Clarke, Deseraé N; Sees, Amanda C; Berger, Andrea L; Kirchner, H Lester; Stametz, Rebecca A; Davis, Daniel

2015-09-01

With growing emphasis on improving the value of health care, there is increased scrutiny of quality outcomes and high health expenditures during the final months of life. The purpose of this project is to answer 1) how do next of kin (NOK) perceive the quality of their loved ones' dying and death; 2) are there patient and NOK characteristics that predict lower quality; and 3) are there structural aspects of care associated with lower quality? A mailed survey was administered to a stratified random sample of NOK of Geisinger Health System patients who had died in the past year. The Quality of Death and Dying, the General Anxiety Disorder seven-item scale, the Patient Health Questionnaire eight-item depression scale, and selected questions from the Toolkit of Instruments to Measure End of Life Care were used. There were 672 respondents. Significant predictors of Quality of Death and Dying score were number of doctors involved in care (P = 0.0415), location of death (P < 0.0001), frequency of receiving confusing or contradictory information (P < 0.0001), illness progression (P = 0.0343), Patient Health Questionnaire-2 score (P = 0.0148), and General Anxiety Disorder seven-item scale score (P < 0.0070). Several findings suggest that factors such as NOK depression and anxiety, prolonged illness, dying in the hospital, receipt of conflicting information, and confusion around the doctor in charge are associated with lower quality of the dying and death experience for NOK. Further investigation is warranted to facilitate high-quality measurement and the use of measurement results to improve care. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Promising System for Selecting Healthy In Vitro–Fertilized Embryos in Cattle

PubMed Central

Sugimura, Satoshi; Akai, Tomonori; Hashiyada, Yutaka; Somfai, Tamás; Inaba, Yasushi; Hirayama, Muneyuki; Yamanouchi, Tadayuki; Matsuda, Hideo; Kobayashi, Shuji; Aikawa, Yoshio; Ohtake, Masaki; Kobayashi, Eiji; Konishi, Kazuyuki; Imai, Kei

2012-01-01

Conventionally, in vitro–fertilized (IVF) bovine embryos are morphologically evaluated at the time of embryo transfer to select those that are likely to establish a pregnancy. This method is, however, subjective and results in unreliable selection. Here we describe a novel selection system for IVF bovine blastocysts for transfer that traces the development of individual embryos with time-lapse cinematography in our developed microwell culture dish and analyzes embryonic metabolism. The system can noninvasively identify prognostic factors that reflect not only blastocyst qualities detected with histological, cytogenetic, and molecular analysis but also viability after transfer. By assessing a combination of identified prognostic factors—(i) timing of the first cleavage; (ii) number of blastomeres at the end of the first cleavage; (iii) presence or absence of multiple fragments at the end of the first cleavage; (iv) number of blastomeres at the onset of lag-phase, which results in temporary developmental arrest during the fourth or fifth cell cycle; and (v) oxygen consumption at the blastocyst stage—pregnancy success could be accurately predicted (78.9%). The conventional method or individual prognostic factors could not accurately predict pregnancy. No newborn calves showed neonatal overgrowth or death. Our results demonstrate that these five predictors and our system could provide objective and reliable selection of healthy IVF bovine embryos. PMID:22590579

Noninvasive Ventilation With vs Without Early Surfactant to Prevent Chronic Lung Disease in Preterm Infants: A Systematic Review and Meta-analysis.

PubMed

Isayama, Tetsuya; Chai-Adisaksopha, Chatree; McDonald, Sarah D

2015-08-01

Controversy exists regarding which of the 2 major strategies currently used to prevent chronic lung disease (CLD) in preterm infants is optimal: noninvasive continuous positive airway pressure (NCPAP) or intubate-surfactant-extubate (INSURE). Preterm infants often require surfactant administration because of respiratory distress syndrome. To evaluate whether early INSURE or NCPAP alone is more effective in preventing CLD, death, or both. We searched the MEDLINE, EMBASE, Cochrane Controlled Trials Register, and Cumulative Index to Nursing and Allied Health Literature databases from their inception to January 2, 2015, along with conference proceedings and trial registrations. Randomized clinical trials that compared early INSURE with NCPAP alone in preterm infants who had never been intubated before the study entry were selected. Among 1761 initially identified articles, 9 trials (1551 infants) were included. Duplicate study selection and data extraction were performed. Meta-analysis was conducted using random-effects models with quality-of-evidence assessment according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Seven main outcomes were selected a priori to be assessed according to GRADE, including a composite outcome of CLD and/or death, CLD alone, death alone, air leakage, severe intraventricular hemorrhage, neurodevelopmental impairment, and a composite outcome of death and/or neurodevelopmental impairment. There were no statistically significant differences between early INSURE and NCPAP alone for all outcomes assessed. However, the relative risk (RR) estimates appeared to favor early INSURE over NCPAP alone, with a 12% RR reduction in CLD and/or death (RR, 0.88; 95% CI, 0.76-1.02; risk difference [RD], -0.04; 95% CI, -0.08 to 0.01; moderate quality of evidence), a 14% decrease in CLD (RR, 0.86; 95% CI, 0.71-1.03; RD, -0.03; 95% CI, -0.06 to 0.01; moderate quality of evidence), and a 50% decrease in air leakage (RR, 0.50; 95% CI, 0.24-1.07; RD, -0.03; 95% CI, -0.06 to 0.00; very low quality of evidence). The sample size was less than the optimal information size. Currently, no evidence suggests that either early INSURE or NCPAP alone is superior to the other. INSURE does not appear to increase CLD and/or death, CLD alone, and air leakage and may reduce these adverse outcomes compared with NCPAP alone. Further adequately powered trials are required.

Youth Risk Behavior Surveillance System: Selected 2011 National Health Risk Behaviors and Health Outcomes by Race/Ethnicity

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2011

2011-01-01

The national Youth Risk Behavior Survey (YRBS) monitors priority health risk behaviors that contribute to the leading causes of death, disability, and social problems among youth and adults in the United States. The national YRBS is conducted every two years during the spring semester and provides data representative of 9th through 12th grade…

Induction of rapid and selective cell necrosis in Drosophila using Bacillus thuringiensis Cry toxin and its silkworm receptor.

PubMed

Obata, Fumiaki; Tanaka, Shiho; Kashio, Soshiro; Tsujimura, Hidenobu; Sato, Ryoichi; Miura, Masayuki

2015-07-08

Genetic ablation of target cells is a powerful tool to study the origins and functions of cells, tissue regeneration, or pathophysiology in a human disease model in vivo. Several methods for selective cell ablation by inducing apoptosis have been established, using exogenous toxins or endogenous proapoptotic genes. However, their application is limited to cells with intact apoptotic machinery. Herein, we established a method for inducing rapid and selective cell necrosis by the pore-forming bacterial toxin Cry1Aa, which is specifically active in cells expressing the Cry1Aa receptor (CryR) derived from the silkworm Bombyx mori. We demonstrated that overexpressing CryR in Drosophila melanogaster tissues induced rapid cell death of CryR-expressing cells only, in the presence of Cry1Aa toxin. Cry/CryR system was effective against both proliferating cells in imaginal discs and polyploid postmitotic cells in the fat body. Live imaging analysis of cell ablation revealed swelling and subsequent osmotic lysis of CryR-positive cells after 30 min of incubation with Cry1Aa toxin. Osmotic cell lysis was still triggered when apoptosis, JNK activation, or autophagy was inhibited, suggesting that Cry1Aa-induced necrotic cell death occurred independently of these cellular signaling pathways. Injection of Cry1Aa into the body cavity resulted in specific ablation of CryR-expressing cells, indicating the usefulness of this method for in vivo cell ablation. With Cry toxins from Bacillus thuringiensis, we developed a novel method for genetic induction of cell necrosis. Our system provides a "proteinous drill" for killing target cells through physical injury of the cell membrane, which can potentially be used to ablate any cell type in any organisms, even those that are resistant to apoptosis or JNK-dependent programmed cell death.

A Competitive Stapled Peptide Screen Identifies a Selective Small Molecule that Overcomes MCL-1-dependent Leukemia Cell Survival

PubMed Central

Cohen, Nicole A.; Stewart, Michelle L.; Gavathiotis, Evripidis; Tepper, Jared L.; Bruekner, Susanne R.; Koss, Brian; Opferman, Joseph T.; Walensky, Loren D.

2012-01-01

SUMMARY Cancer cells hijack BCL-2 family survival proteins to suppress the death effectors and thereby enforce an immortal state. This is accomplished biochemically by an anti-apoptotic surface groove that neutralizes the pro-apoptotic BH3 α-helix of death proteins. Anti-apoptotic MCL-1 in particular has emerged as a ubiquitous resistance factor in cancer. Whereas targeting the BCL-2 anti-apoptotic subclass effectively restores the death pathway in BCL-2-dependent cancer, the development of molecules tailored to the binding specificity of MCL-1 has lagged. We previously discovered that a hydrocarbon-stapled MCL-1 BH3 helix is an exquisitely selective MCL-1 antagonist. By deploying this unique reagent in a competitive screen, we identified an MCL-1 inhibitor molecule that selectively targets the BH3-binding groove of MCL-1, neutralizes its biochemical lockhold on apoptosis, and induces caspase activation and leukemia cell death in the specific context of MCL-1 dependence. PMID:22999885

Jurors' locus of control and defendants' attractiveness in death penalty sentencing.

PubMed

Beckham, Crystal M; Spray, Beverly J; Pietz, Christina A

2007-06-01

The authors examined the relationship between jurors' locus of control and defendants' attractiveness in death penalty sentencing. Ninety-eight participants voluntarily served as mock jurors. The authors administered J. B. Rotter's (1966) Internal-External Locus of Control Scale to participants and then randomly assigned them to a group with either an attractive or an unattractive defendant (represented by photographs). Participants read a murder vignette and selected a punishment--either a lifetime jail sentence or the death penalty-for the defendant. Results indicated that neither jurors' locus of control nor defendants' attractiveness influenced sentencing. However, jurors' age and gender significantly influenced sentencing. Men, with the exception of the youngest men, were more likely than women to choose the death penalty. Additionally, young women were more likely than older women to select the death penalty. The authors discuss the implications of these results for the study of jury behavior and bias.

Suicide Among Veterans in 16 States, 2005 to 2008: Comparisons Between Utilizers and Nonutilizers of Veterans Health Administration (VHA) Services Based on Data From the National Death Index, the National Violent Death Reporting System, and VHA Administrative Records

PubMed Central

Katz, Ira R.; Ignacio, Rosalinda V.; Kemp, Janet

2012-01-01

Objectives. We sought to compare suicide rates among veterans utilizing Veterans Health Administration (VHA) services versus those who did not. Methods. Suicide rates from 2005 to 2008 were estimated for veterans in the 16 states that fully participated in the National Violent Death Reporting System (NVDRS), using data from the National Death Index, NVDRS, and VHA records. Results. Between 2005 and 2008, veteran suicide rates differed by age and VHA utilization status. Among men aged 30 years and older, suicide rates were consistently higher among VHA utilizers. However, among men younger than 30 years, rates declined significantly among VHA utilizers while increasing among nonutilizers. Over these years, an increasing proportion of male veterans younger than 30 years received VHA services, and these individuals had a rising prevalence of diagnosed mental health conditions. Conclusions.The higher rates of suicide for utilizers of VHA among veteran men aged 30 and older were consistent with previous reports about which veterans utilize VHA services. The increasing rates of mental health conditions in utilizers younger than 30 years suggested that the decreasing relative rates in this group were related to the care provided, rather than to selective enrollment of those at lower risk for suicide. PMID:22390582

Agreement on underlying causes of infant death between original records and after investigation: analysis of two biennia in the years 2000.

PubMed

dos Santos, Hellen Geremias; de Andrade, Selma Maffei; Silva, Ana Maria Rigo; de Carvalho, Wladithe Organ; Mesas, Arthur Eumann; González, Alberto Durán

2014-01-01

To analyze the agreement between underlying causes of infant deaths obtained from Death Certificates (DC) with those defined after investigation by the Municipal Committee for the Prevention of Maternal and Infant Mortality (CMPMMI), in Londrina, Paraná State, in the biennia 2000-2001 and 2007-2008. DC of infants and records of investigations were obtained from the CMPMMI. The causes of death registered in both sources were coded according to the International Classification of Diseases, tenth revision (ICD-10), and the underlying causes of deaths were selected. Agreement between underlying causes of deaths was verified by Kappa's (k) test and analyzed according to ICD-10 chapters and blocks of categories in both biennia. In 2000/2001, according to ICD-10 chapters, high agreement rates were observed for conditions originated in the perinatal period (k = 0.85) and for external causes (k = 0.84), while, for congenital malformations, there was a substantial agreement (k = 0.71). In 2007/2008, agreement was considered poor for all analyzed chapters. For blocks of categories, high or substantial agreement rates were observed only in the first biennium for "congenital malformations of the circulatory system" (k = 0.78) and for "other external causes of accidental injury" (k = 0.91). A decrease in agreement between the sources during the study period indicates either an improvement in the process of investigation of infant death by the CMPMMI and/or a worsening in the quality of the DC information.

Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

PubMed

Barabanova, Tatyana; Wiley, Albert L; Bushmanov, Andrey

2012-04-01

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

Death Competence: An Ethical Imperative

ERIC Educational Resources Information Center

Gamino, Louis A.; Ritter, R. Hal, Jr.

2012-01-01

The authors argued that death competence, defined as specialized skill in tolerating and managing clients' problems related to dying, death, and bereavement, is a necessary prerequisite for ethical practice in grief counseling. A selected review of the literature tracing the underpinnings of this concept reveals how a robust construct of death…

Monitoring child mortality through community health worker reporting of births and deaths in Malawi: validation against a household mortality survey.

PubMed

Amouzou, Agbessi; Banda, Benjamin; Kachaka, Willie; Joos, Olga; Kanyuka, Mercy; Hill, Kenneth; Bryce, Jennifer

2014-01-01

The rate of decline in child mortality is too slow in most African countries to achieve the Millennium Development Goal of reducing under-five mortality by two-thirds between 1990 and 2015. Effective strategies to monitor child mortality are needed where accurate vital registration data are lacking to help governments assess and report on progress in child survival. We present results from a test of a mortality monitoring approach based on recording of births and deaths by specially trained community health workers (CHWs) in Malawi. Government-employed community health workers in Malawi are responsible for maintaining a Village Health Register, in which they record births and deaths that occur in their catchment area. We expanded on this system to provide additional training, supervision and incentives. We tested the equivalence between child mortality rates obtained from data on births and deaths collected by 160 randomly-selected and trained CHWs over twenty months in two districts to those computed through a standard household mortality survey. CHW reports produced an under-five mortality rate that was 84% (95%CI: [0.71,1.00]) of the household survey mortality rate and statistically equivalent to it. However, CHW data consistently underestimated under-five mortality, with levels of under-estimation increasing over time. Under-five deaths were more likely to be missed than births. Neonatal and infant deaths were more likely to be missed than older deaths. This first test of the accuracy and completeness of vital events data reported by CHWs in Malawi as a strategy for monitoring child mortality shows promising results but underestimated child mortality and was not stable over the four periods assessed. Given the Malawi government's commitment to strengthen its vital registration system, we are working with the Ministry of Health to implement a revised version of the approach that provides increased support to CHWs.

Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury

PubMed Central

Xie, Cuicui; Ginet, Vanessa; Sun, Yanyan; Koike, Masato; Zhou, Kai; Li, Tao; Li, Hongfu; Li, Qian; Wang, Xiaoyang; Uchiyama, Yasuo; Truttmann, Anita C.; Kroemer, Guido; Puyal, Julien; Blomgren, Klas; Zhu, Changlian

2016-01-01

ABSTRACT Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy. PMID:26727396

Diabetes and ischemic heart disease death in people age 25-54: a multiple-cause-of-death analysis based on over 400 000 deaths from 1990 to 2008 in New York City.

PubMed

Quinones, Adriana; Lobach, Iryna; Maduro, Gil A; Smilowitz, Nathaniel R; Reynolds, Harmony R

2015-02-01

Over the past decade, ischemic heart disease (IHD) mortality trends have been less favorable among adults age 25-54 than age ≥55 years. Disorders associated with IHD such as diabetes, chronic inflammatory and infectious diseases, and cocaine use are important contributors to premature IHD mortality. Multiple-cause-of-death analysis was performed using the New York City (NYC) Vital Statistics database. Frequencies of selected contributing causes on death records with IHD as the underlying cause for decedents age ≥25 were assessed (n = 418,151; 1990-2008). Concurrent Telephone risk-factor surveys (NYC Community Health Survey, Centers for Disease Control Behavioral Risk Factor Survey in New York State) were analyzed. In sum, a prespecified contributing cause was identified on 13.6% of death certificates for IHD decedents age 25-54. Diabetes was reported more frequently for younger IHD decedents (15% of females and 10% of males age 25-54 vs 6% of both sexes age ≥ 55). In contrast, concurrent diabetes prevalence in New York State was 3.4% for those age 25-54 and 13.6% for those age >55 (P < 0.0001). Systemic lupus erythematosus, human immunodeficiency virus, and cocaine were also more likely to contribute to IHD death among younger than older people. Diabetes may be a potent risk factor for IHD death in young people, particularly young women, in whom it was reported on IHD death records at a rate 5× higher than local prevalence. The high frequency of reporting of studied contributing causes in younger IHD decedents may provide a focus for further IHD mortality-reduction efforts in younger adults. © 2015 Wiley Periodicals, Inc.

Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation.

PubMed

Cueva Vargas, Jorge L; Osswald, Ingrid K; Unsain, Nicolas; Aurousseau, Mark R; Barker, Philip A; Bowie, Derek; Di Polo, Adriana

2015-09-02

Loss of vision in glaucoma results from the selective death of retinal ganglion cells (RGCs). Tumor necrosis factor α (TNFα) signaling has been linked to RGC damage, however, the mechanism by which TNFα promotes neuronal death remains poorly defined. Using an in vivo rat glaucoma model, we show that TNFα is upregulated by Müller cells and microglia/macrophages soon after induction of ocular hypertension. Administration of XPro1595, a selective inhibitor of soluble TNFα, effectively protects RGC soma and axons. Using cobalt permeability assays, we further demonstrate that endogenous soluble TNFα triggers the upregulation of Ca(2+)-permeable AMPA receptor (CP-AMPAR) expression in RGCs of glaucomatous eyes. CP-AMPAR activation is not caused by defects in GluA2 subunit mRNA editing, but rather reflects selective downregulation of GluA2 in neurons exposed to elevated eye pressure. Intraocular administration of selective CP-AMPAR blockers promotes robust RGC survival supporting a critical role for non-NMDA glutamate receptors in neuronal death. Our study identifies glia-derived soluble TNFα as a major inducer of RGC death through activation of CP-AMPARs, thereby establishing a novel link between neuroinflammation and cell loss in glaucoma. Tumor necrosis factor α (TNFα) has been implicated in retinal ganglion cell (RGC) death, but how TNFα exerts this effect is poorly understood. We report that ocular hypertension, a major risk factor in glaucoma, upregulates TNFα production by Müller cells and microglia. Inhibition of soluble TNFα using a dominant-negative strategy effectively promotes RGC survival. We find that TNFα stimulates the expression of calcium-permeable AMPA receptors (CP-AMPAR) in RGCs, a response that does not depend on abnormal GluA2 mRNA editing but on selective downregulation of the GluA2 subunit by these neurons. Consistent with this, CP-AMPAR blockers promote robust RGC survival supporting a critical role for non-NMDA glutamate receptors in glaucomatous damage. This study identifies a novel mechanism by which glia-derived soluble TNFα modulates neuronal death in glaucoma. Copyright © 2015 the authors 0270-6474/15/3512088-15$15.00/0.

Assessing the Awareness of Agents Involved in Issuance of Death Certificates About Death Registration Rules in Iran

PubMed Central

Mahdavi, Abdollah; Sedghi, Shahram; Sadoghi, Farahnaz; Azar, Farbod Ebadi Fard

2015-01-01

Introduction: In the death registration system, issuance of death certificate, as a binding rule, is considered among the major necessities of preparation of death statistics. In order to prepare death statistics that are adequately valid for subsequent applications, it is necessary to properly encode death certificates and fully follow rules on causes underlying death. This study aimed to assess the awareness and performance of agents involved in issuance of death certificate in the national death records system. Methods: It was a descriptive cross-sectional research, which was performed from September 2013 to March 2014 on 96 agents involved in issuance of death certificate Imam Khomeini, Alavi, Fatemi and BuAli education and treatment centers of Ardebil University of Medical Sciences. The population included faculty staff physicians, residents and health information management staffs. The research scale was also a researcher-made questionnaire that questioned the demographic information as well as awareness and performance of participants regarding death certificate coding rules. Research data was analyzed based on descriptive statistics and the chi-square test method in the SPSS software at a confidence level of 95%. Findings: A total of 34.42% of participants were aware of the general rules on issuance of death certificates while faculty staff higher specialists (41.67%) and clinical coders (38.34%) with five years of experience demonstrated the highest awareness levels. Only 23 participants (24.6%) were trained to issue death certificates. A total of 76 participants (79.3%) announced their need for learning how to complete death certificate forms on a constant basis. The awareness of participants about the general principle was assessed to be low (30.25%). Moreover, their awareness of selection rules and modification rules was low (27.75%) and moderate (45.25%), respectively. The chi-square test revealed a significant relationship between work experience and awareness of participants about coding rules (P=0.001), but no significant relationship was observed between education and awareness of coding rules (P=0.497). Conclusion: The awareness of participants about rules on coding death causes and their performance in this field was so satisfactory. That is to say, the awareness of faculty staff and health information management staffs was unexpectedly low. Seemingly, lack of adequate training is an international issue that causes mistakes in the recording of information on mortality. Hence, a short-term solution is to train faculty staff and residents and also revise the training provided to health information management staffs. As a long-term solution it is possible to provide related courses to general practitioner students. PMID:26156914

The Role of Oxidative Stress in Apoptosis of Breast Cancer.

DTIC Science & Technology

1995-09-27

supported by studies demonstrating that inappropriate expression of an oncogene, bcl - 2 , prevents cell death and thereby promotes Page _1L ANNUAL REPORT...see Appendix: Baker et al., "Decreased Antioxidant Defense and Increased Oxidant Stress During Dexamethasone-Induced Apoptosis: bcl - 2 Selectively...Alzheimer’s disease. The bcl - 2 oncogene blocks apoptosis in diverse systems and protects cells against oxidative stress- induced damage (Hockenbery et

FastStats: Diabetes

MedlinePlus

... from the National Health Interview Survey Age-adjusted death rates for selected cause of death by sex, race, ... Interview Survey National Home and Hospice Care Survey Mortality data National Center for Chronic Disease Prevention and ...

BAPJ69-4A: a yeast two-hybrid strain for both positive and negative genetic selection.

PubMed

Shaffer, Hally Anne; Rood, Michael Kenneth; Kashlan, Badar; Chang, Eileen I-ling; Doyle, Donald Francis; Azizi, Bahareh

2012-10-01

Genetic selection systems, such as the yeast two-hybrid system, are efficient methods to detect protein-protein and protein-ligand interactions. These systems have been further developed to assess negative interactions, such as inhibition, using the URA3 genetic selection marker. Previously, chemical complementation was used to assess positive selection in Saccharomyces cerevisiae. In this work, a new S. cerevisiae strain, called BAPJ69-4A, containing three selective markers ADE2, HIS3, and URA3 as well as the lacZ gene controlled by Gal4 response elements, was developed and characterized using the retinoid X receptor (RXR) and its ligand 9-cis retinoic acid (9cRA). Further characterization was performed using RXR variants and the synthetic ligand LG335. To assess the functionality of the strain, RXR was compared to the parent strain PJ69-4A in adenine, histidine, and uracil selective media. In positive selection, associating partners that lead to cell growth were observed in all media in the presence of ligand, whereas partners that did not associate due to the absence of ligand displayed no growth. Conversely, in negative selection, partners that did not associate in 5-FOA medium did not display cell death due to the lack of expression of the URA3 gene. The creation of the BAPJ69-4A yeast strain provides a high-throughput selection system, called negative chemical complementation, which can be used for both positive and negative selection, providing a fast, powerful tool for discovering novel ligand receptor pairs for applications in drug discovery and protein engineering. Copyright © 2012 Elsevier B.V. All rights reserved.

Colorectal cancer chemoprevention: the potential of a selective approach.

PubMed

Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

2010-10-01

Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

The National Violent Death Reporting System: an exciting new tool for public health surveillance.

PubMed

Steenkamp, M; Frazier, L; Lipskiy, N; Deberry, M; Thomas, S; Barker, L; Karch, D

2006-12-01

The US does not have a unified system for surveillance of violent deaths. This report describes the National Violent Death Reporting System (NVDRS), a system for collecting data on all violent deaths (homicides, suicides, accidental firearms deaths, deaths of undetermined intent, and deaths from legal intervention, excluding legal executions) in participating states. The NVDRS centralizes data from many sources, providing a more comprehensive picture of violent deaths than would otherwise be available. The NVDRS collects data on victims, suspects, and circumstances related to the violent deaths. Currently, 17 US states participate in the NVDRS; the intention is for the NVDRS to become a truly national system, representing all 50 states, the District of Columbia, and the US territories. This report describes the history of the NVDRS, provides an overview of how the NVDRS functions, and describes future directions.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications. PMID:23335556

Cell death in the thymus--it' s all a matter of contacts.

PubMed

Minter, Lisa M; Osborne, Barbara A

2003-06-01

Apoptosis, or programmed cell death, plays a critical role in shaping the T cell repertoire, deleting unproductive as well as potentially autoreactive T cells. Our understanding of how thymocyte apoptosis is regulated is continually evolving, as new essential modulators of this process are discovered. A conundrum that remains, however, is how signaling through essentially the same receptors and cascades evokes distinct biological responses: death by neglect, positive or negative selection. We hypothesize that the immunological synapse (IS) may be critical to transducing survival signals during thymocyte development, and suggest that factors affecting IS assembly may also influence T cell selection.

Ethics review: Dark angels – the problem of death in intensive care

PubMed Central

2007-01-01

Critical care medicine has expanded the envelope of debilitating disease through the application of an aggressive and invasive care plan, part of which is designed to identify and reverse organ dysfunction before it proceeds to organ failure. For a select patient population, this care plan has been remarkably successful. But because patient selection is very broad, critical care sometimes yields amalgams of life in death: the state of being unable to participate in human life, unable to die, at least in the traditional sense. This work examines the emerging paradox of somatic versus brain death and why it matters to medical science. PMID:17254317

Circumstances surrounding deaths from accidental poisoning 1974-80.

PubMed Central

Craft, A W

1983-01-01

The deaths of 99 children under 5 years of age were studied through the coroners' records. Sixty nine deaths were caused by medicines--most of which were prescribed for mother, were recently dispensed, and currently in use. Household products accounted for 11 deaths, lead poisoning for 6, carbon monoxide for 5 and 'medical mishaps' for 8. Prevention lies in both education and more effective and selective use of child resistant containers. PMID:6870339

26 CFR 1.101-7 - Mortality table used to determine exclusion for deferred payments of life insurance proceeds.

Code of Federal Regulations, 2013 CFR

2013-04-01

... insured's death. If A is 59 years of age at the time of the insured's death, the period with respect to... reference to the interest rate used by the insurance company and the mortality table set forth in § 1.72-7(c... beneficiary, A, at the death of the insured. Upon the insured's death, however, A selects an option for the...

26 CFR 1.101-7 - Mortality table used to determine exclusion for deferred payments of life insurance proceeds.

Code of Federal Regulations, 2011 CFR

2011-04-01

... insured's death. If A is 59 years of age at the time of the insured's death, the period with respect to... reference to the interest rate used by the insurance company and the mortality table set forth in § 1.72-7(c... beneficiary, A, at the death of the insured. Upon the insured's death, however, A selects an option for the...

26 CFR 1.101-7 - Mortality table used to determine exclusion for deferred payments of life insurance proceeds.

Code of Federal Regulations, 2012 CFR

2012-04-01

... insured's death. If A is 59 years of age at the time of the insured's death, the period with respect to... reference to the interest rate used by the insurance company and the mortality table set forth in § 1.72-7(c... beneficiary, A, at the death of the insured. Upon the insured's death, however, A selects an option for the...

26 CFR 1.101-7 - Mortality table used to determine exclusion for deferred payments of life insurance proceeds.

Code of Federal Regulations, 2014 CFR

2014-04-01

... insured's death. If A is 59 years of age at the time of the insured's death, the period with respect to... reference to the interest rate used by the insurance company and the mortality table set forth in § 1.72-7(c... beneficiary, A, at the death of the insured. Upon the insured's death, however, A selects an option for the...

26 CFR 1.101-7 - Mortality table used to determine exclusion for deferred payments of life insurance proceeds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... insured's death. If A is 59 years of age at the time of the insured's death, the period with respect to... reference to the interest rate used by the insurance company and the mortality table set forth in § 1.72-7(c... beneficiary, A, at the death of the insured. Upon the insured's death, however, A selects an option for the...

Influence of obesity on mortality of drivers in severe motor vehicle crashes.

PubMed

Jehle, Dietrich; Gemme, Seth; Jehle, Christopher

2012-01-01

The purpose of the study was to investigate the relationship between obesity and mortality of drivers in severe motor vehicle crashes involving at least one fatality. Fatalities were selected from 155,584 drivers included in the 2000-2005 Fatality Analysis Reporting System. Drivers were stratified by body mass index, confounders were adjusted for, and multiple logistic regression was used to determine the odds ratio (OR) of death in each body mass index class compared with normal weight. The adjusted risk of death from lowest to highest, reported as the OR of death compared with normal weight with 95% confidence intervals, was as follows: (1) overweight (OR, 0.952; 0.911-0.995; P = .0293), (2) slightly obese (OR, 0.996; 0.966-1.026; P = .7758), (3) normal weight, (4) underweight (OR, 1.115; 1.035-1.201; P = .0043), (5) moderately obese (OR, 1.212; 1.128-1.302; P < .0001), and (6) morbidly obese (OR, 1.559; 1.402-1.734; P < .0001). There is an increased risk of death for moderately obese, morbidly obese, and underweight drivers and a decreased risk in overweight drivers. Copyright © 2012 Elsevier Inc. All rights reserved.

The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes

PubMed Central

Indrieri, Alessia; Conte, Ivan; Chesi, Giancarlo; Romano, Alessia; Quartararo, Jade; Tatè, Rosarita; Ghezzi, Daniele; Zeviani, Massimo; Goffrini, Paola; Ferrero, Ileana; Bovolenta, Paola; Franco, Brunella

2013-01-01

Mitochondrial-dependent (intrinsic) programmed cell death (PCD) is an essential homoeostatic mechanism that selects bioenergetically proficient cells suitable for tissue/organ development. However, the link between mitochondrial dysfunction, intrinsic apoptosis and developmental anomalies has not been demonstrated to date. Now we provide the evidence that non-canonical mitochondrial-dependent apoptosis explains the phenotype of microphthalmia with linear skin lesions (MLS), an X-linked developmental disorder caused by mutations in the holo-cytochrome c-type synthase (HCCS) gene. By taking advantage of a medaka model that recapitulates the MLS phenotype we demonstrate that downregulation of hccs, an essential player of the mitochondrial respiratory chain (MRC), causes increased cell death via an apoptosome-independent caspase-9 activation in brain and eyes. We also show that the unconventional activation of caspase-9 occurs in the mitochondria and is triggered by MRC impairment and overproduction of reactive oxygen species (ROS). We thus propose that HCCS plays a key role in central nervous system (CNS) development by modulating a novel non-canonical start-up of cell death and provide the first experimental evidence for a mechanistic link between mitochondrial dysfunction, intrinsic apoptosis and developmental disorders. PMID:23239471

Trends in aortic aneurysm- and dissection-related mortality in the state of São Paulo, Brazil, 1985–2009: multiple-cause-of-death analysis

PubMed Central

2012-01-01

Background Aortic aneurysm and dissection are important causes of death in older people. Ruptured aneurysms show catastrophic fatality rates reaching near 80%. Few population-based mortality studies have been published in the world and none in Brazil. The objective of the present study was to use multiple-cause-of-death methodology in the analysis of mortality trends related to aortic aneurysm and dissection in the state of Sao Paulo, between 1985 and 2009. Methods We analyzed mortality data from the Sao Paulo State Data Analysis System, selecting all death certificates on which aortic aneurysm and dissection were listed as a cause-of-death. The variables sex, age, season of the year, and underlying, associated or total mentions of causes of death were studied using standardized mortality rates, proportions and historical trends. Statistical analyses were performed by chi-square goodness-of-fit and H Kruskal-Wallis tests, and variance analysis. The joinpoint regression model was used to evaluate changes in age-standardized rates trends. A p value less than 0.05 was regarded as significant. Results Over a 25-year period, there were 42,615 deaths related to aortic aneurysm and dissection, of which 36,088 (84.7%) were identified as underlying cause and 6,527 (15.3%) as an associated cause-of-death. Dissection and ruptured aneurysms were considered as an underlying cause of death in 93% of the deaths. For the entire period, a significant increased trend of age-standardized death rates was observed in men and women, while certain non-significant decreases occurred from 1996/2004 until 2009. Abdominal aortic aneurysms and aortic dissections prevailed among men and aortic dissections and aortic aneurysms of unspecified site among women. In 1985 and 2009 death rates ratios of men to women were respectively 2.86 and 2.19, corresponding to a difference decrease between rates of 23.4%. For aortic dissection, ruptured and non-ruptured aneurysms, the overall mean ages at death were, respectively, 63.2, 68.4 and 71.6 years; while, as the underlying cause, the main associated causes of death were as follows: hemorrhages (in 43.8%/40.5%/13.9%); hypertensive diseases (in 49.2%/22.43%/24.5%) and atherosclerosis (in 14.8%/25.5%/15.3%); and, as associated causes, their principal overall underlying causes of death were diseases of the circulatory (55.7%), and respiratory (13.8%) systems and neoplasms (7.8%). A significant seasonal variation, with highest frequency in winter, occurred in deaths identified as underlying cause for aortic dissection, ruptured and non-ruptured aneurysms. Conclusions This study introduces the methodology of multiple-causes-of-death to enhance epidemiologic knowledge of aortic aneurysm and dissection in São Paulo, Brazil. The results presented confer light to the importance of mortality statistics and the need for epidemiologic studies to understand unique trends in our own population. PMID:23046791

Death rates for acquired hypothyroidism and thyrotoxicosis in English populations (1979-2010): comparison of underlying cause and all certified causes.

PubMed

Goldacre, M J; Duncan, M E

2013-03-01

Overt hypothyroidism and thyrotoxicosis have widespread systemic effects and are associated with increased mortality. Most death certificates that include them do not have the thyroid disease coded as the underlying cause of death. To describe regional (1979-2010) and national (1995-2010) trends in mortality rates for acquired hypothyroidism and thyrotoxicosis, analysing all certified causes of death (termed 'mentions') and not just the underlying cause. Analysis of death registration data. Analysis of data for the Oxford region (mentions available from 1979) and English national data (mentions available from 1995). The data were grouped in periods defined by different national rules for selecting the underlying cause of death (1979-83, 1984-92, 1993-2000 and 2001-10) and were also analysed as single calendar years. Mentions mortality for acquired hypothyroidism in the Oxford region declined significantly from 1979 to 2010: the average annual percentage change (AAPC) was -2.6% (95% confidence intervals -3.5, -1.8). Most of the decrease occurred during the 1980s. The AAPC in rates for later years in England (1995-2010) was non-significant at 0.2% (-0.7, 1.0). Mortality rates for thyrotoxicosis decreased significantly: the AAPC was -2.8% (-4.1, -1.5) in the Oxford region and -3.8% (-4.7, -3.0) in England. In England, between 2001 and 2010, hypothyroidism or thyrotoxicosis was coded as the underlying cause of death on, respectively, 17 and 24% of death certificates that included them. Mortality rates for hypothyroidism and thyrotoxicosis have fallen substantially. The fall is probably wholly or mainly a result of improved care.

'A confession of ignorance': deaths from old age and deciphering cause-of-death statistics in Scotland, 1855-1949.

PubMed

Reid, Alice; Garrett, Eilidh; Dibben, Chris; Williamson, Lee

2015-07-03

A large amount of the research undertaken in an attempt to discover the reasons underlying the late nineteenth- and early twentieth-century mortality decline in Britain has relied on the statistics published by the Registrars General. The processes by which individual causes of death are recorded and then processed in order to create the statistics are not, however, well understood. In this article, the authors build on previous work to piece together a time series of causes of death for Scotland, which removes many of the discontinuities encountered in the published statistics that result from the Registrar General deciding to update the nosology, or classification system, which was being used to compile his figures. Having regrouped individual causes of death to 'smooth' the time series, the authors use the new groups to examine the changing causes of death in Scotland for selected age groups, before turning to undertake a detailed examination of mortality amongst those aged 55 or more. The authors find that when deaths from 'old age' in the latter age group are separated from other 'ill-defined' causes, it becomes obvious that there was a 'rebranding' of cause of death. The authors then use individual-level data from two Scottish communities to further dissect the roles played by 'informants' and 'doctors' in this rebranding, in order to see how these roles may have altered over time and what the consequences might be for one's view of how mortality changed in Scotland between 1855 and 1949. Finally, the authors argue that their findings have important implications for some of historical demography's most prominent theories: the McKeown thesis and the theory of epidemiological transition.

Mortality from Musculoskeletal Disorders Including Rheumatoid Arthritis in Southern Sweden: A Multiple-cause-of-death Analysis, 1998-2014.

PubMed

Kiadaliri, Aliasghar A; Turkiewicz, Aleksandra; Englund, Martin

2017-05-01

To assess mortality related to musculoskeletal (MSK) disorders and rheumatoid arthritis (RA), specifically, among adults (aged ≥ 20 yrs) in southern Sweden using the multiple-cause-of-death approach. All death certificates (DC; n = 201,488) from 1998 to 2014 for adults in the region of Skåne were analyzed when mortality from MSK disorders and RA was listed as the underlying and nonunderlying cause of death (UCD/NUCD). Trends in age-standardized mortality rates (ASMR) were evaluated using joinpoint regression, and associated causes were identified by age- and sex-adjusted observed/expected ratios. MSK (RA) was mentioned on 2.8% (0.8%) of all DC and selected as UCD in 0.6% (0.2%), with higher values among women. Proportion of MSK disorder deaths from all deaths increased from 2.7% in 1998 to 3.1% in 2014, and declined from 0.9% to 0.5% for RA. The mean age at death was higher in DC with mention of MSK/RA than in DC without. The mean ASMR for MSK (RA) was 15.5 (4.3) per 100,000 person-years and declined by 1.1% (3.8%) per year during 1998-2014. When MSK/RA were UCD, pneumonia and heart failure were the main NUCD. When MSK/RA were NUCD, the leading UCD were ischemic heart disease and neoplasms. The greatest observed/expected ratios were seen for infectious diseases (including sepsis) and blood diseases. We observed significant reduction in MSK and RA mortality rates and increase in the mean age at death. Further analyses are required to investigate determinants of these improvements in MSK/RA survival and their potential effect on the Swedish healthcare systems.

A comparison of two surveillance systems for deaths related to violent injury

PubMed Central

Comstock, R; Mallonee, S; Jordan, F

2005-01-01

Objective: To compare violent injury death reporting by the statewide Medical Examiner and Vital Statistics Office surveillance systems in Oklahoma. Methods: Using a standard study definition for violent injury death, the sensitivity and predictive value positive (PVP) of the Medical Examiner and Vital Statistics violent injury death reporting systems in Oklahoma in 2001 were evaluated. Results: Altogether 776 violent injury deaths were identified (violent injury death rate: 22.4 per 100 000 population) including 519 (66.9%) suicides, 248 (32.0%) homicides, and nine (1.2%) unintentional firearm deaths. The Medical Examiner system over-reported homicides and the Vital Statistics system under-reported homicides and suicides and over-reported unintentional firearm injury deaths. When compared with the standard, the Medical Examiner and Vital Statistics systems had sensitivities of 99.2% and 90.7% (respectively) and PVPs of 95.0% and 99.1% for homicide, sensitivities of 99.2% and 93.1% and PVPs of 100% and 99.0% for suicide, and sensitivities of 100% and 100% and PVPs of 100% and 31.0% for unintentional firearm deaths. Conclusions: Both the Vital Statistics and Medical Examiner systems contain valuable data and when combined can work synergistically to provide violent injury death information while also serving as quality control checks for each other. Preventable errors within both systems can be reduced by increasing training, addressing sources of human error, and expanding computer quality assurance programming. A standardized nationwide Medical Examiners' coding system and a national violent death reporting system that merges multiple public health and criminal justice datasets would enhance violent injury surveillance and prevention efforts. PMID:15691992

Does the Institution of a Statewide Trauma System Reduce Preventable Mortality and Yield a Positive Return on Investment for Taxpayers?

PubMed

Maxson, Todd; Mabry, Charles D; Sutherland, Michael J; Robertson, Ronald D; Booker, James O; Collins, Terry; Spencer, Horace J; Rinker, Charles F; Sanddal, Teri L; Sanddal, Nels D

2017-04-01

In July 2009, Arkansas began to annually fund $20 million for a statewide trauma system (TS). We studied injury deaths both pre-TS (2009) and post-TS (2013 to 2014), with attention to causes of preventive mortality, societal cost of those preventable mortality deaths, and benefit to tax payers of the lives saved. A multi-specialty trauma-expert panel met and reviewed records of 672 decedents (290 pre-TS and 382 post-TS) who met standardized inclusion criteria, were judged potentially salvageable, and were selected by a proportional sampling of the roughly 2,500 annual trauma deaths. Deaths were adjudicated into sub-categories of nonpreventable and preventable causes. The value of lives lost was calculated for those lives potentially saved in the post-TS period. Total preventable mortality was reduced from 30% of cases pre-TS to 16% of cases studied post-TS, a reduction of 14%. Extrapolating a 14% reduction of preventable mortality to the post-TS study period, using the same inclusion criteria of the post-TS, we calculate that 79 lives were saved in 2013 to 2014 due to the institution of a TS. Using a minimal standard estimate of $100,000 value for a life-year, a lifetime value of $2,365,000 per person was saved. This equates to an economic impact of the lives saved of almost $186 million annually, representing a 9-fold return on investment from the $20 million of annual state funding invested in the TS. The implementation of a TS in Arkansas during a 5-year period resulted in a reduction of the preventable death rate to 16% post-TS, and a 9-fold return on investment by the tax payer. Additional life-saving gains can be expected with ongoing financial support and additional system performance-improvement efforts. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Trimethyltin-induced apoptosis is associated with upregulation of inducible nitric oxide synthase and Bax in a hippocampal cell line

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

Zhang, L.; Li, L.; Prabhakaran, K.

2006-10-01

Trimethyltin (TMT) produces selective neuronal degeneration in the central nervous system (CNS), in which the hippocampus is the most sensitive area. Since previous studies have been conducted in either non-neural cells or mixed primary cultures, an immortalized hippocampal neuronal cell line (HT-22 cell) was used to assess the mechanism and mode of death produced by TMT. The compound produced a time- and concentration-dependent apoptotic death that was caspase-mediated. Excessive generation of reactive oxygen species (ROS) and subsequent reduction of mitochondrial membrane potential ({delta}{psi}{sub m}) were involved in the cytotoxicity{sub .} Scavenging of ROS by a free radical trapping agent ormore » inhibition of the mitochondrial permeability transition (MPT) pore significantly reduced cell death. Additionally, TMT increased expression of inducible nitric oxide synthase (iNOS) by activation of the redox-sensitive transcription factor NF{kappa}B. Pharmacologic inhibition studies showed that the iNOS-mediated NO generation increased expression of Bax and then mitochondrial-mediated apoptosis. It was concluded that excessive ROS generation initiated the apoptotic cell death by upregulating iNOS followed by increased Bax expression which then led to loss of {delta}{psi}{sub m} and caspase-executed cell death. This study is the first to report in a neuronal cell model that TMT stimulates induction of iNOS, which then increases cellular levels of reactive nitrogen species (RNS) to initiate apoptotic death.« less

An integrated national mortality surveillance system for death registration and mortality surveillance, China.

PubMed

Liu, Shiwei; Wu, Xiaoling; Lopez, Alan D; Wang, Lijun; Cai, Yue; Page, Andrew; Yin, Peng; Liu, Yunning; Li, Yichong; Liu, Jiangmei; You, Jinling; Zhou, Maigeng

2016-01-01

In China, sample-based mortality surveillance systems, such as the Chinese Center for Disease Control and Prevention's disease surveillance points system and the Ministry of Health's vital registration system, have been used for decades to provide nationally representative data on health status for health-care decision-making and performance evaluation. However, neither system provided representative mortality and cause-of-death data at the provincial level to inform regional health service needs and policy priorities. Moreover, the systems overlapped to a considerable extent, thereby entailing a duplication of effort. In 2013, the Chinese Government combined these two systems into an integrated national mortality surveillance system to provide a provincially representative picture of total and cause-specific mortality and to accelerate the development of a comprehensive vital registration and mortality surveillance system for the whole country. This new system increased the surveillance population from 6 to 24% of the Chinese population. The number of surveillance points, each of which covered a district or county, increased from 161 to 605. To ensure representativeness at the provincial level, the 605 surveillance points were selected to cover China's 31 provinces using an iterative method involving multistage stratification that took into account the sociodemographic characteristics of the population. This paper describes the development and operation of the new national mortality surveillance system, which is expected to yield representative provincial estimates of mortality in China for the first time.

Apoptosis in the homeostasis of the immune system and in human immune mediated diseases.

PubMed

Giovannetti, A; Pierdominici, M; Di Iorio, A; Cianci, R; Murdaca, G; Puppo, F; Pandolfi, F; Paganelli, R

2008-01-01

The immune system has evolved sophisticated mechanisms controlling the development of responses to dangerous antigens while avoiding unnecessary attacks to innocuous, commensal or self antigens. The risk of autoimmunity is continuously checked and balanced against the risk of succumbing to exogenous infectious agents. It is therefore of paramount importance to understand the molecular events linking the breakdown of tolerance and the development of immunodeficiency. Apoptotic mechanisms are used to regulate the development of thymocytes, the shaping of T cell repertoire, its selection and the coordinate events leading to immune responses in the periphery. Moreover, they are at the heart of the homeostatic controls restoring T cell numbers and establishing T cell memory. T lymphocytes shift continuously from survival to death signals to ensure immune responsiveness without incurring in autoimmune damage. In this review we shall consider some key facts on the relationship of lymphopenia to autoreactivity, the mechanisms controlling positive and negative selection in the thymus, the role of apoptosis in selected primary immunodeficiency states and in systemic and organ-specific autoimmunity, with examples from human diseases and their animal models.

Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality

PubMed Central

Buchanan, Gordon F; Murray, Nicholas M; Hajek, Michael A; Richerson, George B

2014-01-01

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Defects in central control of breathing are important contributors to the pathophysiology of SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined the effect of 5-HT neurone elimination or 5-HT reduction on seizure risk and seizure-induced mortality. Adult Lmx1bf/f/p mice, which lack >99% of 5-HT neurones in the CNS, and littermate controls (Lmx1bf/f) were subjected to acute seizure induction by maximal electroshock (MES) or pilocarpine, variably including electroencephalography, electrocardiography, plethysmography, mechanical ventilation or pharmacological therapy. Lmx1bf/f/p mice had a lower seizure threshold and increased seizure-induced mortality. Breathing ceased during most seizures without recovery, whereas cardiac activity persisted for up to 9 min before terminal arrest. The mortality rate of mice of both genotypes was reduced by mechanical ventilation during the seizure or 5-HT2A receptor agonist pretreatment. The selective serotonin reuptake inhibitor citalopram reduced mortality of Lmx1bf/f but not of Lmx1bf/f/p mice. In C57BL/6N mice, reduction of 5-HT synthesis with para-chlorophenylalanine increased MES-induced seizure severity but not mortality. We conclude that 5-HT neurones raise seizure threshold and decrease seizure-related mortality. Death ensued from respiratory failure, followed by terminal asystole. Given that SUDEP often occurs in association with generalised seizures, some mechanisms causing death in our model might be shared with those leading to SUDEP. This model may help determine the relationship between seizures, 5-HT system dysfunction, breathing and death, which may lead to novel ways to prevent SUDEP. PMID:25107926

Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

PubMed Central

Toscano, Cristiana M.; Alencar, Gizelton P.; Alvarez, Andrés; Valenzuela, Maria T.; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C.; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R.; de Oliveira, Lucia H.

2016-01-01

Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. Methods This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. Results There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively. Conclusion PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE. PMID:27058873

Postmortem brain MRI with selective tissue biopsy as an adjunct to autopsy following neonatal encephalopathy.

PubMed

Nicholl, R M; Balasubramaniam, V P; Urquhart, D S; Sellathurai, N; Rutherford, M A

2007-05-01

Following the death of a neonate it is essential that parents are given full and accurate information about the probable cause of death. Perinatal autopsy often adds new information or may even change the presumed diagnosis [Cartlidge PH, Dawson AT, Stewart JH, Vujanic GM. Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths. Br Med J 1995;310(6973):155-8; Khong TY. Falling neonatal autopsy rates. Br Med J 2002;324(7340):749-50] informing decisions regarding the management of any future pregnancy. Autopsy can be considered the "gold standard" for the identification of antecedent events leading to a neonatal death. However, recent events in the UK have added to an already declining rate in neonatal autopsies [Brodlie M, Laing IA. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. Br Med J 2002;324(7340):761-3]. To try and redress this balance the Chief Medical Officer has recommended that research should be commissioned into the use of non-invasive imaging to provide a similar standard of information [The Chief Medical Officer. The removal, retention and use of human organs and tissues from post mortem examination. London, England: The Stationary Office, Department of Health; 2001]. Previous publications on postmortem MRI have focused largely on investigation of the foetus and of still birth [Griffiths PD, Variend D, Evans M, Jones A, Wilkinson ID, Paley MNJ, et al. Postmortem MR imaging of the fetal and stillborn central nervous system. Am J Neuroradiol 2003;24(1):22-7; Whitby EH, Paley MN, Cohen M, GriffithsPD. Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy? Semin Fetal Neonatal Med 2005;10(5):475-83]. We report our experience on the use of postmortem brain MRI combined with selective tissue biopsy, in six neonatal deaths in the setting of a large district general hospital.

Food groups associated with a reduced risk of 15-year all-cause death.

PubMed

Bongard, V; Arveiler, D; Dallongeville, J; Ruidavets, J-B; Wagner, A; Simon, C; Marécaux, N; Ferrières, J

2016-06-01

Long-term observational cohorts provide the opportunity to investigate the potential impact of dietary patterns on death. We aimed to investigate all-cause death according to the consumption of selected food groups, and then to identify those independently associated with reduced mortality. Population survey of middle-aged men randomly selected in the period 1995-1997 from the general population of three French areas and followed over a median of 14.8 years. Dietary data were collected through a 3-day food record. Cox modeling was used to assess the risk of death according to selected foods groups after extensive adjustment for confounders, including a diet quality index. The study population comprised 960 men (mean age 55.5 ±6.2 years). After a median follow-up of 14.8 (interquartile range 14.3-15.2) years, 150 (15.6%) subjects had died. Food groups that remained independently predictive of a lower risk of death after extensive adjustment were an above-median consumption of milk (adjusted relative risk: 0.61, 95% confidence interval (CI): 0.43-0.86, P-value=0.005), fruits and vegetables (0.68, 0.46-0.98, P-value=0.041) and a moderate consumption of yogurts and cottage cheese (0.50, 95% CI: 0.31-0.81, P-value=0.005), other cheeses (0.62, 0.39-0.97, P-value=0.036) and bread (0.57, 0.37-0.89, P-value=0.014). Besides, there was a nonsignificant trend for a higher risk of death associated with highest sodium intakes. Consumption of food groups that largely match recommendations is associated with a reduced risk of all-cause death in men. A diet providing moderate amounts of diverse food groups appears associated with the highest life expectancy.

Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies--CIBIS and CIBIS II. Cardiac Insufficiency Bisoprolol Study.

PubMed

Leizorovicz, Alain; Lechat, Philippe; Cucherat, Michel; Bugnard, Françoise

2002-02-01

Despite the available evidence from randomized clinical trials, beta-blockers are often not used optimally in patients with congestive heart failure (CHF). This meta-analysis aims at providing a precise and quantitative estimate of the benefit and risks of long-term bisoprolol on major clinical events in patients with CHF, both overall and in selected subgroups. This may help clinicians in their decisions as to whether to prescribe bisoprolol for their individual patients. Meta-analysis was performed of results from the 2 randomized, controlled clinical studies in which bisoprolol was compared with placebo (Cardiac Insufficiency Bisoprolol Study [CIBIS and CIBIS II]), which included 3288 patients with proven CHF. The main outcomes were total death, cardiovascular death, sudden death, hospitalization for heart failure, and myocardial infarction. A highly significant 29.3% relative reduction of death (17%, 40%; P =.00003) was observed, as well as significant risk reduction in cardiovascular death and sudden death in favor of bisoprolol. Also, a highly significant relative reduction of 18.4% (25%, 11%; P =.00001) in hospital admission or death was observed. A similar relative reduction of death was consistently observed in selected subgroups of patients. Bisoprolol prevents major cardiovascular events in patients with CHF with a high benefit-to-risk ratio and can be recommended for these patients.

Evaluating a complex system-wide intervention using the difference in differences method: the Delivering Choice Programme

PubMed Central

Round, Jeff; Drake, Robyn; Kendall, Edward; Addicott, Rachael; Agelopoulos, Nicky; Jones, Louise

2015-01-01

Objectives We report the use of difference in differences (DiD) methodology to evaluate a complex, system-wide healthcare intervention. We use the worked example of evaluating the Marie Curie Delivering Choice Programme (DCP) for advanced illness in a large urban healthcare economy. Methods DiD was selected because a randomised controlled trial was not feasible. The method allows for before and after comparison of changes that occur in an intervention site with a matched control site. This enables analysts to control for the effect of the intervention in the absence of a local control. Any policy, seasonal or other confounding effects over the test period are assumed to have occurred in a balanced way at both sites. Data were obtained from primary care trusts. Outcomes were place of death, inpatient admissions, length of stay and costs. Results Small changes were identified between pre- and post-DCP outputs in the intervention site. The proportion of home deaths and median cost increased slightly, while the number of admissions per patient and the average length of stay per admission decreased slightly. None of these changes was statistically significant. Conclusions Effects estimates were limited by small numbers accessing new services and selection bias in sample population and comparator site. In evaluating the effect of a complex healthcare intervention, the choice of analysis method and output measures is crucial. Alternatives to randomised controlled trials may be required for evaluating large scale complex interventions and the DiD approach is suitable, subject to careful selection of measured outputs and control population. PMID:24644163

Evaluation of the DAVROS (Development And Validation of Risk-adjusted Outcomes for Systems of emergency care) risk-adjustment model as a quality indicator for healthcare

PubMed Central

Wilson, Richard; Goodacre, Steve W; Klingbajl, Marcin; Kelly, Anne-Maree; Rainer, Tim; Coats, Tim; Holloway, Vikki; Townend, Will; Crane, Steve

2014-01-01

Background and objective Risk-adjusted mortality rates can be used as a quality indicator if it is assumed that the discrepancy between predicted and actual mortality can be attributed to the quality of healthcare (ie, the model has attributional validity). The Development And Validation of Risk-adjusted Outcomes for Systems of emergency care (DAVROS) model predicts 7-day mortality in emergency medical admissions. We aimed to test this assumption by evaluating the attributional validity of the DAVROS risk-adjustment model. Methods We selected cases that had the greatest discrepancy between observed mortality and predicted probability of mortality from seven hospitals involved in validation of the DAVROS risk-adjustment model. Reviewers at each hospital assessed hospital records to determine whether the discrepancy between predicted and actual mortality could be explained by the healthcare provided. Results We received 232/280 (83%) completed review forms relating to 179 unexpected deaths and 53 unexpected survivors. The healthcare system was judged to have potentially contributed to 10/179 (8%) of the unexpected deaths and 26/53 (49%) of the unexpected survivors. Failure of the model to appropriately predict risk was judged to be responsible for 135/179 (75%) of the unexpected deaths and 2/53 (4%) of the unexpected survivors. Some 10/53 (19%) of the unexpected survivors died within a few months of the 7-day period of model prediction. Conclusions We found little evidence that deaths occurring in patients with a low predicted mortality from risk-adjustment could be attributed to the quality of healthcare provided. PMID:23605036

AVIRIS study of Death Valley evaporite deposits using least-squares band-fitting methods

NASA Technical Reports Server (NTRS)

Crowley, J. K.; Clark, R. N.

1992-01-01

Minerals found in playa evaporite deposits reflect the chemically diverse origins of ground waters in arid regions. Recently, it was discovered that many playa minerals exhibit diagnostic visible and near-infrared (0.4-2.5 micron) absorption bands that provide a remote sensing basis for observing important compositional details of desert ground water systems. The study of such systems is relevant to understanding solute acquisition, transport, and fractionation processes that are active in the subsurface. Observations of playa evaporites may also be useful for monitoring the hydrologic response of desert basins to changing climatic conditions on regional and global scales. Ongoing work using Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data to map evaporite minerals in the Death Valley salt pan is described. The AVIRIS data point to differences in inflow water chemistry in different parts of the Death Valley playa system and have led to the discovery of at least two new North American mineral occurrences. Seven segments of AVIRIS data were acquired over Death Valley on 31 July 1990, and were calibrated to reflectance by using the spectrum of a uniform area of alluvium near the salt pan. The calibrated data were subsequently analyzed by using least-squares spectral band-fitting methods, first described by Clark and others. In the band-fitting procedure, AVIRIS spectra are fit compared over selected wavelength intervals to a series of library reference spectra. Output images showing the degree of fit, band depth, and fit times the band depth are generated for each reference spectrum. The reference spectra used in the study included laboratory data for 35 pure evaporite spectra extracted from the AVIRIS image cube. Additional details of the band-fitting technique are provided by Clark and others elsewhere in this volume.

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

PubMed Central

2012-01-01

Background There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults. Methods The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH): ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable. Results Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association. Conclusions Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome selection/ascertainment, and methodology. Accounting for confounding and selection biases in these studies is of particular concern. Future studies should address this and other methodological issues. PMID:22682429

Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells.

PubMed

Marcos-Campos, I; Asín, L; Torres, T E; Marquina, C; Tres, A; Ibarra, M R; Goya, G F

2011-05-20

In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The number of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1-5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min and the viability of the blank DCs (i.e. without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH(2)(+)) or negative (COOH(-)) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the number of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

PubMed

Rosner, S; Ginzler, E M; Diamond, H S; Weiner, M; Schlesinger, M; Fries, J F; Wasner, C; Medsger, T A; Ziegler, G; Klippel, J H; Hadler, N M; Albert, D A; Hess, E V; Spencer-Green, G; Grayzel, A; Worth, D; Hahn, B H; Barnett, E V

1982-06-01

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

A magnetic switch for the control of cell death signalling in in vitro and in vivo systems

NASA Astrophysics Data System (ADS)

Cho, Mi Hyeon; Lee, Eun Jung; Son, Mina; Lee, Jae-Hyun; Yoo, Dongwon; Kim, Ji-Wook; Park, Seung Woo; Shin, Jeon-Soo; Cheon, Jinwoo

2012-12-01

The regulation of cellular activities in a controlled manner is one of the most challenging issues in fields ranging from cell biology to biomedicine. Nanoparticles have the potential of becoming useful tools for controlling cell signalling pathways in a space and time selective fashion. Here, we have developed magnetic nanoparticles that turn on apoptosis cell signalling by using a magnetic field in a remote and non-invasive manner. The magnetic switch consists of zinc-doped iron oxide magnetic nanoparticles (Zn0.4Fe2.6O4), conjugated with a targeting antibody for death receptor 4 (DR4) of DLD-1 colon cancer cells. The magnetic switch, in its On mode when a magnetic field is applied to aggregate magnetic nanoparticle-bound DR4s, promotes apoptosis signalling pathways. We have also demonstrated that the magnetic switch is operable at the micrometre scale and that it can be applied in an in vivo system where apoptotic morphological changes of zebrafish are successfully induced.

Use of comorbidity measures to predict the risk of death in Brazilian in-patients.

PubMed

Martins, Monica

2010-06-01

To assess the use of comorbidity measures to predict the risk of death in Brazilian in-patients. Data from the Sistema de Informações Hospitalares do Sistema Unico de Saúde (Unified Health System Hospital Information System) were used, which enables only one secondary diagnosis to be recorded. A total of 1,607,697 hospitalizations were selected, all of which occurred in Brazil, between 2003 and 2004, and whose main diagnoses were: ischemic heart disease, congestive cardiac failure, stroke and pneumonia. Charlson Index and Elixhauser comorbidities were the comorbidity measures used. In addition, the simple record of a certain secondary diagnosis was also used. Logistic regression was applied to assess the impact of comorbidity measures on the estimate of risk of death. The baseline model included the following variables: age, sex and main diagnosis. Models to predict death were assessed, based on C-statistic and Hosmer-Lemeshow test. Hospital mortality rate was 10.4% and mean length of stay was 5.7 days. The majority (52%) of hospitalizations occurred among men and mean age was 62.6 years. Of all hospitalizations, 5.4% included a recorded secondary diagnosis, although the odds ratio between death and presence of comorbidity was 1.93. The baseline model showed a discriminatory capacity (C-statistic) of 0.685. The improvement in the models, attributed to the introduction of comorbidity indices, was poor, equivalent to zero when C-statistic with only two digits was considered. Although the introduction of three comorbidity measures in distinct models to predict death improved the predictive capacity of the baseline model, the values obtained are still considered insufficient. The accuracy of this type of measure is influenced by the completeness of the source of information. In this sense, high underreporting of secondary diagnosis, in addition to the well-known lack of space to note down this type of information in the Sistema de Informações Hospitalares, are the main explanatory factors for the results found.

Mortality Predictors in Patients with Severe Dengue in the State of Amazonas, Brazil

PubMed Central

Pinto, Rosemary Costa; de Castro, Daniel Barros; de Albuquerque, Bernardino Cláudio; Sampaio, Vanderson de Souza; dos Passos, Ricardo Augusto; da Costa, Cristiano Fernandes; Sadahiro, Megumi; Braga, José Ueleres

2016-01-01

Dengue is a major public health problem in tropical and subtropical areas worldwide. There is a lack of information on the risk factors for death due to severe dengue fever in developing countries, including Brazil where the state of Amazonas is located. This knowledge is important for decision making and the implementation of effective measures for patient care. This study aimed to identify factors associated with death among patients with severe dengue, in Amazonas from 2001 to 2013. We conducted a retrospective cohort study based on secondary data from the epidemiological surveillance of dengue provided by the Fundação de Vigilância em Saúde do Amazonas, FVS (Health Surveillance Foundation) of the Secretaria de Saúde do Amazonas, SUSAM (Health Secretariat of the State of Amazonas). Data on dengue cases were obtained from the SINAN (Notifiable Diseases Information System) and SIM (Mortality Information System) databases. We selected cases of severe dengue with laboratory confirmation, including dengue-related deaths of residents in the state of Amazonas from January 1, 2001, to December 31, 2013. The explanatory variables analyzed were sex, age, level of education, spontaneous hemorrhagic manifestations, plasma extravasation and platelet count. Patients who died due to severe dengue had more hematuria, gastrointestinal bleeding, and thrombocytopenia than the survivors. Considering the simultaneous effects of demographic and clinical characteristics with a multiple logistic regression model, it was observed that the factors associated with death were age >55 years (odds ratio [OR] 4.98), gastrointestinal bleeding (OR 10.26), hematuria (OR 5.07), and thrombocytopenia (OR 2.55). Gastrointestinal bleeding was the clinical sign most strongly associated with death, followed by hematuria and age >55 years. The study results showed that the best predictor of death from severe dengue is based on the characteristic of age >55 years, together with the clinical signs of gastrointestinal bleeding, hematuria, and low platelet count. PMID:27564084

Mortality Predictors in Patients with Severe Dengue in the State of Amazonas, Brazil.

PubMed

Pinto, Rosemary Costa; Castro, Daniel Barros de; Albuquerque, Bernardino Cláudio de; Sampaio, Vanderson de Souza; Passos, Ricardo Augusto Dos; Costa, Cristiano Fernandes da; Sadahiro, Megumi; Braga, José Ueleres

2016-01-01

Dengue is a major public health problem in tropical and subtropical areas worldwide. There is a lack of information on the risk factors for death due to severe dengue fever in developing countries, including Brazil where the state of Amazonas is located. This knowledge is important for decision making and the implementation of effective measures for patient care. This study aimed to identify factors associated with death among patients with severe dengue, in Amazonas from 2001 to 2013. We conducted a retrospective cohort study based on secondary data from the epidemiological surveillance of dengue provided by the Fundação de Vigilância em Saúde do Amazonas, FVS (Health Surveillance Foundation) of the Secretaria de Saúde do Amazonas, SUSAM (Health Secretariat of the State of Amazonas). Data on dengue cases were obtained from the SINAN (Notifiable Diseases Information System) and SIM (Mortality Information System) databases. We selected cases of severe dengue with laboratory confirmation, including dengue-related deaths of residents in the state of Amazonas from January 1, 2001, to December 31, 2013. The explanatory variables analyzed were sex, age, level of education, spontaneous hemorrhagic manifestations, plasma extravasation and platelet count. Patients who died due to severe dengue had more hematuria, gastrointestinal bleeding, and thrombocytopenia than the survivors. Considering the simultaneous effects of demographic and clinical characteristics with a multiple logistic regression model, it was observed that the factors associated with death were age >55 years (odds ratio [OR] 4.98), gastrointestinal bleeding (OR 10.26), hematuria (OR 5.07), and thrombocytopenia (OR 2.55). Gastrointestinal bleeding was the clinical sign most strongly associated with death, followed by hematuria and age >55 years. The study results showed that the best predictor of death from severe dengue is based on the characteristic of age >55 years, together with the clinical signs of gastrointestinal bleeding, hematuria, and low platelet count.

On the role of phosphatidylinositol 3-kinase, protein kinase b/Akt, and glycogen synthase kinase-3β in photodynamic injury of crayfish neurons and glial cells.

PubMed

Komandirov, Maxim A; Knyazeva, Evgeniya A; Fedorenko, Yulia P; Rudkovskii, Mikhail V; Stetsurin, Denis A; Uzdensky, Anatoly B

2011-10-01

Photodynamic treatment that causes intense oxidative stress and cell death is currently used in neurooncology. However, along with tumor cells, it may damage healthy neurons and glia. To study the involvement of signaling processes in photodynamic injury or protection of neurons and glia, we used crayfish mechanoreceptor consisting of a single neuron surrounded by glial cells. It was photosensitized with alumophthalocyanine Photosens. Application of specific inhibitors showed that phosphatidylinositol 3-kinase did not participate in photoinduced death of neurons and glia. Akt was involved in photoinduced necrosis but not in apoptosis of neurons and glia. Glycogen synthase kinase-3β participated in photoinduced apoptosis of glial cells and in necrosis of neurons. Therefore, phosphatidylinositol 3-kinase/protein kinase Akt/glycogen synthase kinase-3β pathway was not involved as a whole in photodynamic injury of crayfish neurons and glia but its components, Akt and glycogen synthase kinase-3β, independently and cell specifically regulated death of neurons and glial cells. According to these data, necrosis in this system was a controlled but not a non-regulated cell death mode. The obtained results may be used for the search of pharmacological agents selectively modulating death and survival of normal neurons and glial cells during photodynamic therapy of brain tumors.

Fatal injuries in the slums of Nairobi and their risk factors: results from a matched case-control study.

PubMed

Ziraba, Abdhalah Kasiira; Kyobutungi, Catherine; Zulu, Eliya Msiyaphazi

2011-06-01

Injuries contribute significantly to the rising morbidity and mortality attributable to non-communicable diseases in the developing world. Unfortunately, active injury surveillance is lacking in many developing countries, including Kenya. This study aims to describe and identify causes of and risk factors for fatal injuries in two slums in Nairobi city using a demographic surveillance system framework. The causes of death are determined using verbal autopsies. We used a nested case-control study design with all deaths from injuries between 2003 and 2005 as cases. Two controls were randomly selected from the non-injury deaths over the same period and individually matched to each case on age and sex. We used conditional logistic regression modeling to identity individual- and community-level factors associated with fatal injuries. Intentional injuries accounted for about 51% and unintentional injuries accounted for 49% of all injuries. Homicides accounted for 91% of intentional injuries and 47% of all injury-related deaths. Firearms (23%) and road traffic crashes (22%) were the leading single causes of deaths due to injuries. About 15% of injuries were due to substance intoxication, particularly alcohol, which in this community comes from illicit brews and is at times contaminated with methanol. Results suggest that in the pervasively unsafe and insecure environment that characterizes the urban slums, ethnicity, residence, and area level factors contribute significantly to the risk of injury-related mortality.

Emergency department utilization and subsequent prescription drug overdose death

PubMed Central

Brady, Joanne E.; DiMaggio, Charles J.; Keyes, Katherine M.; Doyle, John J.; Richardson, Lynne D.; Li, Guohua

2015-01-01

Purpose Prescription drug overdose (PDO) deaths are a critical public health problem in the United States. This study aims to assess the association between emergency department (ED) utilization patterns in a cohort of ED patients and the risk of subsequent unintentional PDO mortality. Methods Using data from the New York Statewide Planning and Research Cooperative System for 2006–2010, a nested case-control design was used to examine the relationship between ED utilization patterns in New York State residents of age 18–64 years and subsequent PDO death. Results The study sample consisted of 2732 case patients who died of PDO and 2732 control ED patients who were selected through incidence density sampling. With adjustment for demographic characteristics, and diagnoses of pain, substance abuse, and psychiatric disorders, the estimated odds ratios of PDO death relative to one ED visit or less in the previous year were 4.90 (95% confidence interval [CI]: 4.50–5.34) for those with two ED visits, 16.61 (95% CI: 14.72–18.75) for those with three ED visits, and 48.24 (95% CI: 43.23–53.83) for those with four ED visits or more. Conclusions Frequency of ED visits is strongly associated with the risk of subsequent PDO death. Intervention programs targeting frequent ED users are warranted to reduce PDO mortality. PMID:25935710

The Selection of Death Place Among Patients Receiving Hospital-Based Palliative Care Service in Taiwan.

PubMed

Ho, Ching-Sung

2018-05-01

To analyze the selection of a place to die and its related factors in patients who received hospice shared care service in Taiwan. This study included patients who received hospice shared care service in a metropolitan hospital as the research participants. A total of 172 questionnaires were collected, and 146 of them were used as valid samples for analysis. This study applied the multivariate logistic regression analysis to assess the significance of independent variables associated with the selection of place of death. The results revealed that 52.6% of the patients select hospital as the place to end their life, while 43.8% of them select their home as the place of death. Furthermore, younger adult patients (<65), those who with a higher educational level (≥10 years), and those with a clear cognizance of the disease progression tended to select hospital as the place to spend their last days. The research disclosed that more patients with the hospice shared care service prefer hospital to their home as the place to die. In order to provide end-of-life care for patients with low cost and appropriate treatment, it is important to understand the related sociodemographic factors and the need of the patients to provide well-designed hospice/specialist palliative care regimen.

The Relation Between Death Attitude and Distress: Tolerance, Aggression, and Anger.

PubMed

Esnaashari, Fatemeh; Kargar, Flor Rezaei

2018-06-01

The aim of this research was to determine the relation between death attitude and distress tolerance and aggression and anger. For this, 135 subjects among 7,535 professional and specialist members of the Iran National Library were selected using convenience sampling method. They replied to Death Attitudes Profile-Revised, distress tolerance questionnaire, and aggression questionnaire. The results showed that the attitudes of approach acceptance, neutral acceptance, and escape acceptance had positive relation to distress tolerance and negative relation to aggression and anger while the attitudes of fear of death and death avoidance had negative relation to distress tolerance and positive relation to aggression and anger. Furthermore, all death attitudes predicted distress tolerance. But only the attitudes of approach acceptance, escape acceptance, fear of death, and death avoidance predicted aggression, and only approach acceptance, neutral acceptance, fear of death, and death avoidance predicted anger.

The Difficulty of Selecting the NANDA-I Nursing Diagnosis (2015-2017) of "Death Anxiety" in Japan.

PubMed

Shimomai, Kimiyo; Furukawa, Hidetoshi; Kuroda, Yuko; Fukuda, Kazuaki; Masuda, Mitsumi; Koizumi, Junko

2018-01-01

The purpose of our study was to clarify any difficulties or problems that exist in Japanese healthcare sites regarding the selection of death anxiety as a nursing diagnosis. This study was a qualitative, inductive research design. The semistructured interviews were conducted on the participants who were nurses and had 3 or more years of clinical experience in Japan. Results showed four categories: "The Japanese have a culture of avoiding death," "It is extremely difficult to match diagnostic indicators and related factors with specific patient cases," "Other diagnoses exist that are effective and enable proactive intervention," and "The definition of death anxiety and the meaning of its diagnostic indicators are unintelligible." It is thought that nursing diagnoses that reflect specific cultural backgrounds require definitions appropriate to each country and appropriate revisions to diagnostic indicators. © 2016 NANDA International, Inc.

The Fas/CD95 Receptor Regulates the Death of Autoreactive B Cells and the Selection of Antigen-Specific B Cells

PubMed Central

Koncz, Gabor; Hueber, Anne-Odile

2012-01-01

Cell death receptors have crucial roles in the regulation of immune responses. Here we review recent in vivo data confirming that the Fas death receptor (TNFSR6) on B cells is important for the regulation of autoimmunity since the impairment of only Fas function on B cells results in uncontrolled autoantibody production and autoimmunity. Fas plays a role in the elimination of the non-specific and autoreactive B cells in germinal center, while during the selection of antigen-specific B cells different escape signals ensure the resistance to Fas-mediated apoptosis. Antigen-specific survival such as BCR or MHCII signal or coreceptors (CD19) cooperating with BCR inhibits the formation of death inducing signaling complex. Antigen-specific survival can be reinforced by antigen-independent signals of IL-4 or CD40 overproducing the anti-apoptotic members of the Bcl-2 family proteins. PMID:22848207

System care improves trauma outcome: patient care errors dominate reduced preventable death rate.

PubMed

Thoburn, E; Norris, P; Flores, R; Goode, S; Rodriguez, E; Adams, V; Campbell, S; Albrink, M; Rosemurgy, A

1993-01-01

A review of 452 trauma deaths in Hillsborough County, Florida, in 1984 documented that 23% of non-CNS trauma deaths were preventable and occurred because of inadequate resuscitation or delay in proper surgical care. In late 1988 Hillsborough County organized a County Trauma Agency (HCTA) to coordinate trauma care among prehospital providers and state-designated trauma centers. The purpose of this study was to review county trauma deaths after the inception of the HCTA to determine the frequency of preventable deaths. 504 trauma deaths occurring between October 1989 and April 1991 were reviewed. Through committee review, 10 deaths were deemed preventable; 2 occurred outside the trauma system. Of the 10 deaths, 5 preventable deaths occurred late in severely injured patients. The preventable death rate has decreased to 7.0% with system care. The causes of preventable deaths have changed from delayed or inadequate intervention to postoperative care errors.

Inhibition of the ubiquitin-proteasome system by natural products for cancer therapy.

PubMed

Tsukamoto, Sachiko; Yokosawa, Hideyoshi

2010-08-01

The ubiquitin-proteasome system plays a critical role in selective protein degradation and regulates almost all cellular events such as cell cycle progression, signal transduction, cell death, immune responses, metabolism, protein quality control, development, and neuronal function. The recent approval of bortezomib, a synthetic proteasome inhibitor, for the treatment of relapsed multiple myeloma has opened the way to the discovery of drugs targeting the proteasome and ubiquitinating and deubiquitinating enzymes as well as the delivery system. To date, various synthetic and natural products have been reported to inhibit the components of the ubiquitin-proteasome system. Here, we review natural products targeting the ubiquitin-proteasome system as well as synthetic compounds with potent inhibitory effects. Georg Thieme Verlag KG Stuttgart-New York.

Evaluation of active mortality surveillance system data for monitoring hurricane-related deaths-Texas, 2008.

PubMed

Choudhary, Ekta; Zane, David F; Beasley, Crystal; Jones, Russell; Rey, Araceli; Noe, Rebecca S; Martin, Colleen; Wolkin, Amy F; Bayleyegn, Tesfaye M

2012-08-01

The Texas Department of State Health Services (DSHS) implemented an active mortality surveillance system to enumerate and characterize hurricane-related deaths during Hurricane Ike in 2008. This surveillance system used established guidelines and case definitions to categorize deaths as directly, indirectly, and possibly related to Hurricane Ike. The objective of this study was to evaluate Texas DSHS' active mortality surveillance system using US Centers for Disease Control and Prevention's (CDC) surveillance system evaluation guidelines. Using CDC's Updated Guidelines for Surveillance System Evaluation, the active mortality surveillance system of the Texas DSHS was evaluated. Data from the active mortality surveillance system were compared with Texas vital statistics data for the same time period to estimate the completeness of reported disaster-related deaths. From September 8 through October 13, 2008, medical examiners (MEs) and Justices of the Peace (JPs) in 44 affected counties reported deaths daily by using a one-page, standardized mortality form. The active mortality surveillance system identified 74 hurricane-related deaths, whereas a review of vital statistics data revealed only four deaths that were hurricane-related. The average time of reporting a death by active mortality surveillance and vital statistics was 14 days and 16 days, respectively. Texas's active mortality surveillance system successfully identified hurricane-related deaths. Evaluation of the active mortality surveillance system suggested that it is necessary to collect detailed and representative mortality data during a hurricane because vital statistics do not capture sufficient information to identify whether deaths are hurricane-related. The results from this evaluation will help improve active mortality surveillance during hurricanes which, in turn, will enhance preparedness and response plans and identify public health interventions to reduce future hurricane-related mortality rates.

Female labor force participation and female mortality in Wisconsin 1974-1978.

PubMed

Passannante, M R; Nathanson, C A

1985-01-01

The following research question is addressed in the study: what effect will the entrance of women into the labor force have on female mortality rates for all causes of death combined as well as specific causes relating to occupational stress, behavioral factors and physical hazards associated with occupation? This question is examined through comparisons of age, marital status and occupation-specific death rates for all causes of death combined and for selected causes of death. Death certificates provided by the Wisconsin Bureau of Health Statistics for the years 1974-1978 and population data provided by the 1976 Survey of Income and Education were used to construct death rates. The death rates of the white civilian female population of Wisconsin 16-64 years of age were examined using exploratory data analysis techniques (schematic plots and median polish) and standard errors. In general, the death rates of women in the labor force are substantially lower than those of housewives. These results may indicate that the role of housewife exposes women to health hazards. In addition, the results of this study may suggest some selectivity of healthy women into the labor force or a protective effect of labor force participation. In a limited number of instances, labor force participants' mortality rates exceed those of housewives. In the 60-64 year old population, white-collar workers, specifically, sales workers, managers and professionals, experience significantly higher death rates than housewives. In addition, specific groups of labor force participants experience significantly higher death rates than housewives for accidental deaths (i.e. laborers 16-44 and 45-54), deaths due to heart disease (i.e. laborers 45-54 and sales workers 60-64) and deaths due to malignant neoplasms (i.e. white-collar workers 60-64 years of age). The possibility that these instances indicate the direction of future mortality trends should be considered.

When dinner is dangerous: toxic frogs elicit species-specific responses from a generalist snake predator.

PubMed

Phillips, Ben; Shine, Richard

2007-12-01

In arms races between predators and prey, some evolved tactics are unbeatable by the other player. For example, many types of prey are inedible because they have evolved chemical defenses. In this case, prey death removes any selective advantage of toxicity to the prey but not the selective advantage to a predator of being able to consume the prey. In the absence of effective selection for postmortem persistence of the toxicity then, some chemical defenses probably break down rapidly after prey death. If so, predators can overcome the toxic defense simply by waiting for that breakdown before consuming the prey. Floodplain death adders (Acanthophis praelongus) are highly venomous frog-eating elapid snakes native to northern Australia. Some of the frogs they eat are nontoxic (Litoria nasuta), others produce gluelike mucus when seized by a predator (Limnodynastes convexiusculus), and one species (Litoria dahlii) is dangerously toxic to snakes. Both the glue and the toxin degrade within about 20 min of prey death. Adders deal with these prey types in different and highly stereotyped ways: they consume nontoxic frogs directly but envenomate and release the other taxa, waiting until the chemical defense loses its potency before consuming the prey.

Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

MedlinePlus

... MB] Related FastStats Asthma More Data Age-adjusted death rates for selected causes of death, by sex, race, ... table 18 [PDF – 9.8 MB] COPD-related Mortality by Sex and Race Among Adults Aged 25 ...

WikiLeaks and Iraq Body Count: the sum of parts may not add up to the whole-a comparison of two tallies of Iraqi civilian deaths.

PubMed

Carpenter, Dustin; Fuller, Tova; Roberts, Les

2013-06-01

Introduction The number of civilians killed in Iraq following the 2003 invasion has proven difficult to measure and contentious in recent years. The release of the Wikileaks War Logs (WL) has created the potential to conduct a sensitivity analysis of the commonly-cited Iraq Body Count's (IBC's) tally, which is based on press, government, and other public sources. Hypothesis The 66,000 deaths reported in the Wikileaks War Logs are mostly the same events as those previously reported in the press and elsewhere as tallied by iraqbodycount.org. A systematic random sample of 2500 violent fatal War Log incidents was selected and evaluated to determine whether these incidents were also found in IBC's press-based listing. Each selected event was ranked on a scale of 0 (no match present) to 3 (almost certainly matched) with regard to the likelihood it was listed in the IBC database. Of the two thousand four hundred and nine War Log records, 488 (23.8%) were found to have likely matches in IBC records. Events that killed more people were far more likely to appear in both datasets, with 94.1% of events in which ≥20 people were killed being likely matches, as compared with 17.4% of singleton killings. Because of this skew towards the recording of large events in both datasets, it is estimated that 2035 (46.3%) of the 4394 deaths reported in the Wikileaks War Logs had been previously reported in IBC. Passive surveillance systems, widely seen as incomplete, may also be selective in the types of events detected in times of armed conflict. Bombings and other events during which many people are killed, and events in less violent areas, appear to be detected far more often, creating a skewed image of the mortality profile in Iraq. Members of the press and researchers should be hesitant to draw conclusions about the nature or extent of violence from passive surveillance systems of low or unknown sensitivity.

Medical examiner/death investigator training requirements in state medical examiner systems.

PubMed

Prahlow, J A; Lantz, P E

1995-01-01

Comprehensive and properly performed investigation of suspicious, unusual, unnatural, and various natural deaths is necessary to maintain the health, safety, and well-being of society as a whole. Adequate investigation requires the combined efforts and cooperation of law-enforcement and other public-service agencies, medical professionals, and those within the forensic community. As such, the "death investigator" plays a crucial role in the investigation process. These front-line investigators, whether they be coroners, medical examiners, physicians, other medical professionals, or lay-people, are required to make important decisions which have far-reaching consequences on how death investigation cases proceed. Death investigation practices vary greatly among medico-legal jurisdictions. A recent publication has categorized state death investigation systems by type of system. In an attempt to better delineate death investigation practices with specific regard to investigators' training and continuing education requirements, we surveyed the 20 systems categorized as state medical examiner systems and the five states with combined state medical examiner and county coroner/medical examiner systems. We present our findings and make recommendations which address the attributes and deficiencies of current death investigation practices.

The double mortality burden among adults in Addis Ababa, Ethiopia, 2006-2009.

PubMed

Misganaw, Awoke; Mariam, Damen Haile; Araya, Tekebash

2012-01-01

In Ethiopia, lack of reliable data on causes of death prevents full understanding of the double mortality burden of communicable and noncommunicable diseases. Our objective was to help bridge this research gap by analyzing surveillance data on causes of death in Addis Ababa. Burial surveillance identified 58,010 deaths in Addis Ababa from 2006 through 2009, of which 49,309 were eligible for verbal autopsies, a method of interviewing caregivers of the deceased about the circumstances, signs, and symptoms preceding death. We randomly selected 10% from the eligible sample, of whom 91% were defined as adults (aged ≥ 15 y). Verbal autopsies were completed and causes of death were assigned for 3,709 adults. Overall, 51% (95% confidence interval [CI], 49.7%-52.9%) of deaths were attributed to noncommunicable diseases, 42% (95% CI, 40.6%-43.8%) to communicable diseases, and 6% (95% CI, 5.5%-7.0%) to injuries. Similar proportions of male and female deaths were caused by noncommunicable and communicable diseases. Adults aged 55 to 84 were more likely, and those aged 15 to 44 were less likely, to die from noncommunicable diseases compared with the age group 85 or older. Premature deaths (defined as earlier than age 65) from noncommunicable diseases were mainly due to certain cancers, type 1 and type 2 diabetes, hypertension, stroke, and genitourinary disease. Noncommunicable diseases are the leading cause of death among adults in Addis Ababa, where the health care system is still geared toward addressing communicable diseases. Health policy attention is needed to remedy this situation. This observed double mortality burden is unlikely to be unique to Addis Ababa and provides new insight into the epidemiological transition in urban Ethiopia. Nationwide studies should be conducted in Ethiopia to examine the pattern of epidemiological transition and the magnitude of double mortality burden.

Fall-related mortality in southern Sweden: a multiple cause of death analysis, 1998-2014.

PubMed

Kiadaliri, Aliasghar A; Rosengren, Björn E; Englund, Martin

2017-10-22

To investigate temporal trend in fall mortality among adults (aged ≥20 years) in southern Sweden using multiple cause of death data. We examined all death certificates (DCs, n=2 01 488) in adults recorded in the Skåne region during 1998-2014. We identified all fall deaths using International Statistical Classification of Diseases (ICD)-10 codes (W00-W19) and calculated the mortality rates by age and sex. Temporal trends were evaluated using joinpoint regression and associated causes were identified by age-adjusted and sex-adjusted observed/expected ratios. Falls were mentioned on 1.0% and selected as underlying cause in 0.7% of all DCs, with the highest frequency among those aged ≥70 years. The majority (75.6%) of fall deaths were coded as unspecified fall (ICD-10 code: W19) followed by falling on or from stairs/steps (7.7%, ICD-10 code: W10) and other falls on the same level (6.3%, ICD-10 code: W18). The mean age at fall deaths increased from 77.5 years in 1998-2002 to 82.9 years in 2010-2014 while for other deaths it increased from 78.5 to 79.8 years over the same period. The overall mean age-standardised rate of fall mortality was 8.3 and 4.0 per 1 00 000 person-years in men and women, respectively, and increased by 1.7% per year in men and 0.8% per year in women during 1998-2014. Head injury and diseases of the circulatory system were recorded as contributing cause on 48.7% of fall deaths. There is an increasing trend of deaths due to falls in southern Sweden. Further investigations are required to explain this observation particularly among elderly men. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An investigation of bias in a study of nuclear shipyard workers.

PubMed

Greenberg, E R; Rosner, B; Hennekens, C; Rinsky, R; Colton, T

1985-02-01

The authors examined discrepant findings between a 1978 proportional mortality study and a 1981 cohort study of workers at the Portsmouth, New Hampshire, Naval Shipyard to determine whether the healthy worker effect, selection bias, or measurement bias could explain why only the proportional mortality study found excess cancer deaths among nuclear workers. Lower mortality from noncancer causes in nuclear workers (the healthy worker effect) partly accounted for the observed elevated cancer proportional mortality. More important, however, was measurement bias which occurred in the proportional mortality study when nuclear workers who had not died of cancer were misclassified as not being nuclear workers based on information from their next of kin, thereby creating a spurious association. Although the proportional mortality study was based on a small sample of all deaths occurring in the cohort, selection bias did not contribute materially to the discrepant results for total cancer deaths. With regard to leukemia, misclassification of occupation in the proportional mortality study and disagreement about cause of death accounted for some of the reported excess deaths.

Genetic architecture and balancing selection: the life and death of differentiated variants.

PubMed

Llaurens, Violaine; Whibley, Annabel; Joron, Mathieu

2017-05-01

Balancing selection describes any form of natural selection, which results in the persistence of multiple variants of a trait at intermediate frequencies within populations. By offering up a snapshot of multiple co-occurring functional variants and their interactions, systems under balancing selection can reveal the evolutionary mechanisms favouring the emergence and persistence of adaptive variation in natural populations. We here focus on the mechanisms by which several functional variants for a given trait can arise, a process typically requiring multiple epistatic mutations. We highlight how balancing selection can favour specific features in the genetic architecture and review the evolutionary and molecular mechanisms shaping this architecture. First, balancing selection affects the number of loci underlying differentiated traits and their respective effects. Control by one or few loci favours the persistence of differentiated functional variants by limiting intergenic recombination, or its impact, and may sometimes lead to the evolution of supergenes. Chromosomal rearrangements, particularly inversions, preventing adaptive combinations from being dissociated are increasingly being noted as features of such systems. Similarly, due to the frequency of heterozygotes maintained by balancing selection, dominance may be a key property of adaptive variants. High heterozygosity and limited recombination also influence associated genetic load, as linked recessive deleterious mutations may be sheltered. The capture of deleterious elements in a locus under balancing selection may reinforce polymorphism by further promoting heterozygotes. Finally, according to recent genomewide scans, balanced polymorphism might be more pervasive than generally thought. We stress the need for both functional and ecological studies to characterize the evolutionary mechanisms operating in these systems. © 2017 John Wiley & Sons Ltd.

A Dying Child in the Family: The Child's and Sibling's Perspective. Selected Papers, Number 60.

ERIC Educational Resources Information Center

Said, John

Children and adolescents have different understandings of death. For the baby, death is equated with separation. For toddlers, grief occurs when they realize the person is not returning. The preschool child who tends to live in the present with no clear concept of past or future will not understand the finality. Around ages 4 and 5, death is often…

Measles deaths in Nepal: estimating the national case-fatality ratio.

PubMed

Joshi, Anand B; Luman, Elizabeth T; Nandy, Robin; Subedi, Bal K; Liyanage, Jayantha B L; Wierzba, Thomas F

2009-06-01

To estimate the case-fatality ratio (CFR) for measles in Nepal, determine the role of risk factors, such as political instability, for measles mortality, and compare the use of a nationally representative sample of outbreaks versus routine surveillance or a localized study to establish the national CFR (nCFR). This was a retrospective study of measles cases and deaths in Nepal. Through two-stage random sampling, we selected 37 districts with selection probability proportional to the number of districts in each region, and then randomly selected within each district one outbreak among all those that had occurred between 1 March and 1 September 2004. Cases were identified by interviewing a member of each and every household and tracing contacts. Bivariate analyses were performed to assess the risk factors for a high CFR and determine the time from rash onset until death. Each factor's contribution to the CFR was determined through multivariate logistic regression. From the number of measles cases and deaths found in the study we calculated the total number of measles cases and deaths for all of Nepal during the study period and in 2004. We identified 4657 measles cases and 64 deaths in the study period and area. This yielded a total of about 82 000 cases and 900 deaths for all outbreaks in 2004 and a national CFR of 1.1% (95% confidence interval, CI: 0.5-2.3). CFR ranged from 0.1% in the eastern region to 3.4% in the mid-western region and was highest in politically insecure areas, in the Ganges plains and among cases < 5 years of age. Vitamin A treatment and measles immunization were protective. Most deaths occurred during the first week of illness. To our knowledge, this is the first CFR study based on a nationally representative sample of measles outbreaks. Routine surveillance and studies of a single outbreak may not yield an accurate nCFR. Increased fatalities associated with political insecurity are a challenge for health-care service delivery. The short period from disease onset to death and reduced mortality from treatment with vitamin A suggest the need for rapid, field-based treatment early in the outbreak.

Deaths from Falls Among Persons Aged ≥65 Years - United States, 2007-2016.

PubMed

Burns, Elizabeth; Kakara, Ramakrishna

2018-05-11

Deaths from unintentional injuries are the seventh leading cause of death among older adults (1), and falls account for the largest percentage of those deaths. Approximately one in four U.S. residents aged ≥65 years (older adults) report falling each year (2), and fall-related emergency department visits are estimated at approximately 3 million per year.* In 2016, a total of 29,668 U.S. residents aged ≥65 years died as the result of a fall (age-adjusted rate †  = 61.6 per 100,000), compared with 18,334 deaths (47.0) in 2007. To evaluate this increase, CDC produced age-adjusted rates and trends for deaths from falls among persons aged ≥65 years, by selected characteristics (sex, age group, race/ethnicity, and urban/rural status) and state from 2007 to 2016. The rate of deaths from falls increased in the United States by an average of 3.0% per year during 2007-2016, and the rate increased in 30 states and the District of Columbia (DC) during that period. In eight states, the rate of deaths from falls increased for a portion of the study period. The rate increased in almost every demographic category included in the analysis, with the largest increase per year among persons aged ≥85 years. Health care providers should be aware that deaths from falls are increasing nationally among older adults but that falls are preventable. Falls and fall prevention should be discussed during annual wellness visits, when health care providers can assess fall risk, educate patients about falls, and select appropriate interventions.

Repeated Exposure of Epithelial Cells to Apoptotic Cells Induces the Specific Selection of an Adaptive Phenotype: Implications for Tumorigenesis.

PubMed

Feng, Lanfei; Vujicic, Snezana; Dietrich, Michael E; Litbarg, Natalia; Setty, Suman; Antoni, Angelika; Rauch, Joyce; Levine, Jerrold S

2018-05-16

The consequences of apoptosis extend beyond mere death of the cell. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits PTEC proliferation, growth, and survival. Here we tested the hypothesis that continual exposure to apoptotic targets can induce a phenotypic change in responding PTECs, as in other instances of natural selection. In particular, we demonstrate that repeated exposure to apoptotic targets leads to emergence of a PTEC line (denoted BU.MPT SEL ) resistant to apoptotic target-induced death. Resistance is exquisitely specific. Not only are BU.MPT SEL responders fully resistant to apoptotic target-induced death (~85% survival versus <10% survival of non-selected cells), but do so while retaining sensitivity to all other target-induced responses, including inhibition of proliferation and growth. Moreover, the resistance of BU.MPT SEL responders is specific to target-induced apoptosis, as apoptosis in response to other suicidal stimuli occurs normally. Comparison of the signaling events induced by apoptotic target exposure in selected versus non-selected responders indicated that the acquired resistance of BU.MPT SEL cells lies in a regulatory step affecting the generation of the pro-apoptotic protein, truncated BH3 interacting-domain death agonist (tBID), most likely at the level of BID cleavage by caspase-8. This specific adaptation has especial relevance for cancer, in which the prominence and persistence of cell death entail magnification of the post-mortem effects of apoptotic cells. Just as cancer cells acquire specific resistance to chemotherapeutic agents, we propose that cancer cells may also adapt to their ongoing exposure to apoptotic targets. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Using natural products to promote caspase-8-dependent cancer cell death.

PubMed

Tewary, Poonam; Gunatilaka, A A Leslie; Sayers, Thomas J

2017-02-01

The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides as TRAIL sensitizers. Finally, we will suggest synergistic approaches for combining active withanolides with various forms of immunotherapy to promote cancer cell death and an effective antitumor immune response.

Cannabinoid Receptor Type 1 Agonist ACEA Protects Neurons from Death and Attenuates Endoplasmic Reticulum Stress-Related Apoptotic Pathway Signaling.

PubMed

Vrechi, Talita A; Crunfli, Fernanda; Costa, Andressa P; Torrão, Andréa S

2018-05-01

Neurodegeneration is the result of progressive destruction of neurons in the central nervous system, with unknown causes and pathological mechanisms not yet fully elucidated. Several factors contribute to neurodegenerative processes, including neuroinflammation, accumulation of neurotoxic factors, and misfolded proteins in the lumen of the endoplasmic reticulum (ER). Endocannabinoid signaling has been pointed out as an important modulatory system in several neurodegeneration-related processes, inhibiting the inflammatory response and increasing neuronal survival. Thus, we investigated the presumptive protective effect of the selective cannabinoid type 1 (CB1) receptor agonist arachidonyl-2'-chloroethylamide (ACEA) against inflammatory (lipopolysaccharide, LPS) and ER stress (tunicamycin) stimuli in an in vitro neuronal model (Neuro-2a neuroblastoma cells). Cell viability analysis revealed that ACEA was able to protect against cell death induced by LPS and tunicamycin. This neuroprotective effect occurs via the CB1 receptor in the inflammation process and via the transient receptor potential of vanilloid type-1 (TRPV1) channel in ER stress. Furthermore, the immunoblotting analyses indicated that the neuroprotective effect of ACEA seems to involve the modulation of eukaryotic initiation factor 2 (eIF2α), transcription factor C/EBP homologous protein (CHOP), and caspase 12, as well as the survival/death p44/42 MAPK, ERK1/2-related signaling pathways. Together, these data suggest that the endocannabinoid system is a potential therapeutic target in neurodegenerative processes, especially in ER-related neurodegenerative diseases.

Surveillance for Violent Deaths - National Violent Death Reporting System, 17 States, 2013.

PubMed

Lyons, Bridget H; Fowler, Katherine A; Jack, Shane P D; Betz, Carter J; Blair, Janet M

2016-08-19

In 2013, more than 57,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 17 U.S. states for 2013. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2013. NVDRS collects data from participating states regarding violent deaths obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, supplemental homicide reports, hospital data, and crime laboratory data). This report includes data from 17 states that collected statewide data for 2013 (Alaska, Colorado, Georgia, Kentucky, Maryland, Massachusetts, North Carolina, New Jersey, New Mexico, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin). NVDRS collates documents for each death and links deaths that are related (e.g., multiple homicides, a homicide followed by a suicide, or multiple suicides) from a single incident. For 2013, a total of 18,765 fatal incidents involving 19,251 deaths were captured by NVDRS in the 17 states included in this report. The majority (66.2%) of deaths were suicides, followed by homicides (23.2%), deaths of undetermined intent (8.8%), deaths involving legal intervention (1.2%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force, excluding legal executions), and unintentional firearm deaths (<1%). (The term legal intervention is a classification incorporated into the International Classification of Diseases, Tenth Revision [ICD-10] and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Suicides occurred at higher rates among males, non-Hispanic whites, American Indian/Alaska Natives, persons aged 45-64 years, and males aged ≥75 years. Suicides were preceded primarily by a mental health, intimate partner, or physical health problem or a crisis during the previous or upcoming 2 weeks. Homicide rates were higher among males and persons aged 15-44 years; rates were highest among non-Hispanic black males. Homicides primarily were precipitated by arguments and interpersonal conflicts, occurrence in conjunction with another crime, or were related to intimate partner violence (particularly for females). A known relationship between a homicide victim and a suspected perpetrator was most likely either that of an acquaintance or friend or an intimate partner. Legal intervention death rates were highest among males and persons aged 20-24 years and 30-34 years; rates were highest among non-Hispanic black males. Precipitating factors for the majority of legal intervention deaths were another crime, a mental health problem, or a recent crisis. Deaths of undetermined intent occurred at the highest rates among males and persons aged <1 year and 45-54 years. Substance abuse and mental or physical health problems were the most common circumstances preceding deaths of undetermined intent. Unintentional firearm death rates were higher among males, non-Hispanic whites, and persons aged persons aged 15-19 and 55-64 years; these deaths were most often precipitated by a person unintentionally pulling the trigger while playing with a firearm or while hunting. This report provides a detailed summary of data from NVDRS for 2013. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected persons aged <65 years, males, and certain minority populations. For homicides and suicides, intimate partner problems, interpersonal conflicts, mental health problems, and recent crises were primary precipitating factors. NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths. For example, Utah Violent Death Reporting System (VDRS) data were used to develop policies that support children of intimate partner homicide victims, Colorado VDRS data to develop a web-based suicide prevention program targeting middle-aged men, and Rhode Island VDRS data to help guide suicide prevention efforts at workplaces. The continued development and expansion of NVDRS to include all U.S. states, territories, and the District of Columbia are essential to public health efforts to reduce the impact of violence.

Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

PubMed Central

Joubert, Fourie; Harrison, Claudia M; Koegelenberg, Riaan J; Odendaal, Christiaan J; de Beer, Tjaart AP

2009-01-01

Background Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties. Methods A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available. Results An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum. Conclusion The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties. PMID:19642978

Photochemical Targeting Of Phagocytic Trabecular Meshwork Cells Using Chlorin E6 Coupled Microspheres

NASA Astrophysics Data System (ADS)

Latina, M. A.; Kobsa, P. H.; Rakestraw, S. L.; Crean, E. A.; Hasan, T.; Yarmush, M. L.

1989-03-01

We have investigated a novel and efficient delivery system utilizing photosensitizer-coupled-latex microspheres to photochemically target and kill phagocytic trabecular meshwork (TM) cells. TM cells are the most actively phagocytic cells within the anterior chamber of the eye and are located within an optically accessible discrete band. This delivery system, along with the property of cell photocytosis, will achieve double selectivity by combining preferential localization of the photosensitizer to the target cells with spatial localization of illumination on the target cells. All experiments were performed with preconfluent bovine TM cells, 3rd to 4th passage, plated in 15 mm wells. Chlorin e6 monoethylene diamine monoamide was conjugated to the surface of 1.0 Am MX Duke Scientific fluorescent latex microspheres. Spectroscopic analysis revealed an average of 1.3 x 10 -17 moles of chlorin e6 per microsphere. TM cells were incubated for 18 hours with 5 x 10 7 microspheres/ml in MEM with 10% FCS, washed with MEM, and irradiated through fresh media using an argon-pumped dye laser emitting .2 W at 660 nm. A dose-survival study indicated that energy doses of 10 J/cm2 or greater resulted in greater than 95% cell death as determined by ethidium bromide exclusion. Cell death could be demonstrated as early as 4 hours post-irradiation. TM cells incubated with a solution of chlorin e6 at a concentration equal to that conjugated to the microspheres showed no cell death. Unirradiated controls also showed no cell death.

Effect of marital status on death rates. Part 2: Transient mortality spikes

NASA Astrophysics Data System (ADS)

Richmond, Peter; Roehner, Bertrand M.

2016-05-01

We examine what happens in a population when it experiences an abrupt change in surrounding conditions. Several cases of such ;abrupt transitions; for both physical and living social systems are analyzed from which it can be seen that all share a common pattern. First, a steep rising death rate followed by a much slower relaxation process during which the death rate decreases as a power law. This leads us to propose a general principle which can be summarized as follows: ;Any abrupt change in living conditions generates a mortality spike which acts as a kind of selection process;. This we term the Transient Shock conjecture. It provides a qualitative model which leads to testable predictions. For example, marriage certainly brings about a major change in personal and social conditions and according to our conjecture one would expect a mortality spike in the months following marriage. At first sight this may seem an unlikely proposition but we demonstrate (by three different methods) that even here the existence of mortality spikes is supported by solid empirical evidence.

Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

PubMed

Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

2017-06-01

Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43 Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43 Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

Starvation induced cell death in autophagy-defective yeast mutants is caused by mitochondria dysfunction.

PubMed

Suzuki, Sho W; Onodera, Jun; Ohsumi, Yoshinori

2011-02-25

Autophagy is a highly-conserved cellular degradation and recycling system that is essential for cell survival during nutrient starvation. The loss of viability had been used as an initial screen to identify autophagy-defective (atg) mutants of the yeast Saccharomyces cerevisiae, but the mechanism of cell death in these mutants has remained unclear. When cells grown in a rich medium were transferred to a synthetic nitrogen starvation media, secreted metabolites lowered the extracellular pH below 3.0 and autophagy-defective mutants mostly died. We found that buffering of the starvation medium dramatically restored the viability of atg mutants. In response to starvation, wild-type (WT) cells were able to upregulate components of the respiratory pathway and ROS (reactive oxygen species) scavenging enzymes, but atg mutants lacked this synthetic capacity. Consequently, autophagy-defective mutants accumulated the high level of ROS, leading to deficient respiratory function, resulting in the loss of mitochondria DNA (mtDNA). We also showed that mtDNA deficient cells are subject to cell death under low pH starvation conditions. Taken together, under starvation conditions non-selective autophagy, rather than mitophagy, plays an essential role in preventing ROS accumulation, and thus in maintaining mitochondria function. The failure of response to starvation is the major cause of cell death in atg mutants.

Selective Survival of Nonpigmented Mutants in Pasteurella Pestis Cultures

DTIC Science & Technology

Differential death rates that occur under certain conditions in cultures of Pasteurella pestis result in dramatic population shifts. Comparable...growth and death rates were observed for pigmented inocula and their nonpigmented variants in a casein digest (NZ-Amine, Sheffield, Type A) medium

Evaluation of Active Mortality Surveillance System Data for Monitoring Hurricane-Related Deaths—Texas, 2008

PubMed Central

Choudhary, Ekta; Zane, David F.; Beasley, Crystal; Jones, Russell; Rey, Araceli; Noe, Rebecca S.; Martin, Colleen; Wolkin, Amy F.; Bayleyegn, Tesfaye M.

2015-01-01

Introduction The Texas Department of State Health Services (DSHS) implemented an active mortality surveillance system to enumerate and characterize hurricane-related deaths during Hurricane Ike in 2008. This surveillance system used established guidelines and case definitions to categorize deaths as directly, indirectly, and possibly related to Hurricane Ike. Objective The objective of this study was to evaluate Texas DSHS’ active mortality surveillance system using US Centers for Disease Control and Prevention’s (CDC) surveillance system evaluation guidelines. Methods Using CDC’s Updated Guidelines for Surveillance System Evaluation, the active mortality surveillance system of the Texas DSHS was evaluated. Data from the active mortality surveillance system were compared with Texas vital statistics data for the same time period to estimate the completeness of reported disaster-related deaths. Results From September 8 through October 13, 2008, medical examiners (MEs) and Justices of the Peace (JPs) in 44 affected counties reported deaths daily by using a one-page, standardized mortality form. The active mortality surveillance system identified 74 hurricane-related deaths, whereas a review of vital statistics data revealed only four deaths that were hurricane-related. The average time of reporting a death by active mortality surveillance and vital statistics was 14 days and 16 days, respectively. Conclusions Texas’s active mortality surveillance system successfully identified hurricane-related deaths. Evaluation of the active mortality surveillance system suggested that it is necessary to collect detailed and representative mortality data during a hurricane because vital statistics do not capture sufficient information to identify whether deaths are hurricane-related. The results from this evaluation will help improve active mortality surveillance during hurricanes which, in turn, will enhance preparedness and response plans and identify public health interventions to reduce future hurricane-related mortality rates. PMID:22800916

On the paradigm of altruistic suicide in the unicellular world.

PubMed

Nedelcu, Aurora M; Driscoll, William W; Durand, Pierre M; Herron, Matthew D; Rashidi, Armin

2011-01-01

Altruistic suicide is best known in the context of programmed cell death (PCD) in multicellular individuals, which is understood as an adaptive process that contributes to the development and functionality of the organism. After the realization that PCD-like processes can also be induced in single-celled lineages, the paradigm of altruistic cell death has been extended to include these active cell death processes in unicellular organisms. Here, we critically evaluate the current conceptual framework and the experimental data used to support the notion of altruistic suicide in unicellular lineages, and propose new perspectives. We argue that importing the paradigm of altruistic cell death from multicellular organisms to explain active death in unicellular lineages has the potential to limit the types of questions we ask, thus biasing our understanding of the nature, origin, and maintenance of this trait. We also emphasize the need to distinguish between the benefits and the adaptive role of a trait. Lastly, we provide an alternative framework that allows for the possibility that active death in single-celled organisms is a maladaptive trait maintained as a byproduct of selection on pro-survival functions, but that could-under conditions in which kin/group selection can act-be co-opted into an altruistic trait. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Investigation of selective induction of breast cancer cells to death with treatment of plasma-activated medium

NASA Astrophysics Data System (ADS)

Hashizume, Hiroshi; Tanaka, Hiromasa; Nakamura, Kae; Kano, Hiroyuki; Ishikawa, Kenji; Kikkawa, Fumitaka; Mizuno, Masaaki; Hori, Masaru

2015-09-01

The applications of plasma in medicine have much attention. We previously showed that plasma-activated medium (PAM) induced glioblastoma cells to apoptosis. However, it has not been elucidated the selectivity of PAM in detail. In this study, we investigated the selective effect of PAM on the death of human breast normal and cancer cells, MCF10A and MCF7, respectively, and observed the selective death with fluorescent microscopy. For the investigation of cell viability with PAM treatment, we prepared various PAMs according to the strengths, and treated each of cells with PAMs. Week PAM treatment only decreased the viability of MCF7 cells, while strong PAM treatment significantly affected both viabilities of MCF7 and MCF10A cells. For the fluorescent observation, we prepared the mixture of MCF7 and fluorescent-probed MCF10A cells, and seeded them. After the treatment of PAMs, the images showed that only MCF7 cells damaged in the mixture with week PAM treatment. These results suggested that a specific range existed with the selective effect in the strength of PAM. This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas ``Plasma Medical Innovation'' Grant No. 24108002 and 24108008 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

The Value of Outsourcing Selected Cases in a Medical Examiner Population: A 10-Year Experience.

PubMed

McCleskey, Brandi C; Reilly, Stephanie D; Atherton, Dan

2017-01-01

Due to increasing caseloads and inadequate staffing, the burden on Coroner/Medical Examiner Offices to comply with recommended autopsy limits for forensic pathologists (FPs) has been difficult. Since 2006, pathologists at the University of Alabama at Birmingham have performed select autopsies for the Alabama Department of Forensic Sciences. Each case was reviewed by a state FP and scene investigator to determine appropriateness for referral. All referred cases received full postmortem examination including microscopic examination and collection of toxicological samples, and toxicology was ordered by the referring FP as appropriate. The final cause and manner of death were determined by the referring state FP after review of all findings. A majority of the 421 cases were ruled accidental deaths (233), most due to drug toxicity. Of the 178 natural deaths, 118 were attributed to cardiovascular disease. Outsourcing select forensic cases can be educational and an effective tool to manage workflow without compromising quality. © 2016 American Academy of Forensic Sciences.

Evaluating a complex system-wide intervention using the difference in differences method: the Delivering Choice Programme.

PubMed

Round, Jeff; Drake, Robyn; Kendall, Edward; Addicott, Rachael; Agelopoulos, Nicky; Jones, Louise

2015-03-01

We report the use of difference in differences (DiD) methodology to evaluate a complex, system-wide healthcare intervention. We use the worked example of evaluating the Marie Curie Delivering Choice Programme (DCP) for advanced illness in a large urban healthcare economy. DiD was selected because a randomised controlled trial was not feasible. The method allows for before and after comparison of changes that occur in an intervention site with a matched control site. This enables analysts to control for the effect of the intervention in the absence of a local control. Any policy, seasonal or other confounding effects over the test period are assumed to have occurred in a balanced way at both sites. Data were obtained from primary care trusts. Outcomes were place of death, inpatient admissions, length of stay and costs. Small changes were identified between pre- and post-DCP outputs in the intervention site. The proportion of home deaths and median cost increased slightly, while the number of admissions per patient and the average length of stay per admission decreased slightly. None of these changes was statistically significant. Effects estimates were limited by small numbers accessing new services and selection bias in sample population and comparator site. In evaluating the effect of a complex healthcare intervention, the choice of analysis method and output measures is crucial. Alternatives to randomised controlled trials may be required for evaluating large scale complex interventions and the DiD approach is suitable, subject to careful selection of measured outputs and control population. 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.

Determinants of neonatal death with emphasis on health care during pregnancy, childbirth and reproductive history.

PubMed

Kassar, Samir B; Melo, Ana M C; Coutinho, Sônia B; Lima, Marilia C; Lira, Pedro I C

2013-01-01

To identify risk factors for neonatal mortality, focusing on factors related to assistance care during the prenatal period, childbirth, and maternal reproductive history. This was a case-control study conducted in Maceió, Northeastern Brazil. The sample consisted of 136 cases and 272 controls selected from official Brazilian databases. The cases consisted of all infants who died before 28 days of life, selected from the Mortality Information System, and the controls were survivors during this period, selected from the Information System on Live Births, by random drawing among children born on the same date of the case. Household interviews were conducted with mothers. The logistic regression analysis identified the following as determining factors for death in the neonatal period: mothers with a history of previous children who died in the first year of life (OR=3.08), hospitalization during pregnancy (OR=2.48), inadequate prenatal care (OR=2.49), lack of ultrasound examination during prenatal care (OR=3.89), transfer of the newborn to another unit after birth (OR=5.06), admittance of the newborn at the ICU (OR=5.00), and low birth weight (OR=2.57). Among the socioeconomic conditions, there was a greater chance for neonatal mortality in homes with fewer residents (OR=1.73) and with no children younger than five years (OR=10.10). Several factors that were associated with neonatal mortality in this study may be due to inadequate care during the prenatal period and childbirth, and inadequate newborn care, all of which can be modified. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

[The modern approaches to organization of delivery system in Nizhniy Novgorod].

PubMed

Ryzhova, N K; Lazarev, V N

2014-01-01

The article presents data concerning reproductive demographic processes in Nizhniy Novgorod. The numbers of women of fertility age and indicator of maternity mortality were selected as objects for analysis. The structure of causes of maternal mortality is presented and on its basis the corresponding classification was developed. To prevent maternal losses the development of specialized centers was proposed and implementation of high-tech blood-preserving techniques as well. The routing and accompaniment of women being in critical ("closer to death") conditions are considered.

Tuberculosis and HIV are the leading causes of adult death in northwest Ethiopia: evidence from verbal autopsy data of Dabat health and demographic surveillance system, 2007-2013.

PubMed

Kebede, Yigzaw; Andargie, Gashaw; Gebeyehu, Abebaw; Awoke, Tadesse; Yitayal, Mezgebu; Mekonnen, Solomon; Wubshet, Mamo; Azmeraw, Temesgen; Lakew, Yihunie; Alemu, Kassahun

2017-01-01

Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system. Causes of death were classified and prepared based on the International Classification of Diseases (ICD-10). The cause of a death was ascertained based on an interview with next of kin or other caregivers using a standardized questionnaire that draws information on signs, symptoms, medical history, and circumstances preceding death. The cause of death, or the sequence of causes that led to death, is assigned based on the data collected by the questionnaire. The complete VA questionnaires were given to two blinded physicians and reviewed independently. A third physician was assigned to review the case when disagreements in diagnosis arose. Communicable diseases (519 deaths [48.0%]), non-communicable diseases (377 deaths [34.8%]), and external causes (113 deaths [10.4%]) were the main causes of death between 2007 and 2013. Of communicable diseases, tuberculosis (207 deaths [19.7%]), HIV/AIDS (96 deaths [8.9%]) and meningitis (76 deaths [7.0%]) were the most common causes of death. Tuberculosis, HIV/AIDS, and meningitis were the most common causes of deaths among adults. Death due to non-communicable diseases showed an increasing trend. Increasing community awareness of infections and their interrelationships, tuberculosis case finding, effective local TB programs, successful treatment, and interventions for HIV are supremely important.

Tuberculosis and HIV are the leading causes of adult death in northwest Ethiopia: evidence from verbal autopsy data of Dabat health and demographic surveillance system, 2007-2013.

PubMed

Kebede, Yigzaw; Andargie, Gashaw; Gebeyehu, Abebaw; Awoke, Tadesse; Yitayal, Mezgebu; Mekonnen, Solomon; Wubshet, Mamo; Azmeraw, Temesgen; Lakew, Yihunie; Alemu, Kassahun

2017-07-17

Reliable data on causes of death form the basis for building evidence on health policy, planning, monitoring, and evaluation. In Ethiopia, the majority of deaths occur at home and civil registration systems are not yet functional. The main objective of verbal autopsy (VA) is to describe the causes of death at the community or population level where civil registration and death certification systems are weak and where most people die at home without having had contact with the health system. Causes of death were classified and prepared based on the International Classification of Diseases (ICD-10). The cause of a death was ascertained based on an interview with next of kin or other caregivers using a standardized questionnaire that draws information on signs, symptoms, medical history, and circumstances preceding death. The cause of death, or the sequence of causes that led to death, is assigned based on the data collected by the questionnaire. The complete VA questionnaires were given to two blinded physicians and reviewed independently. A third physician was assigned to review the case when disagreements in diagnosis arose. Communicable diseases (519 deaths [48.0%]), non-communicable diseases (377 deaths [34.8%]), and external causes (113 deaths [10.4%]) were the main causes of death between 2007 and 2013. Of communicable diseases, tuberculosis (207 deaths [19.7%]), HIV/AIDS (96 deaths [8.9%]) and meningitis (76 deaths [7.0%]) were the most common causes of death. Tuberculosis, HIV/AIDS, and meningitis were the most common causes of deaths among adults. Death due to non-communicable diseases showed an increasing trend. Increasing community awareness of infections and their interrelationships, tuberculosis case finding, effective local TB programs, successful treatment, and interventions for HIV are supremely important.

The National Violent Death Reporting System: overview and future directions.

PubMed

Blair, Janet M; Fowler, Katherine A; Jack, Shane P D; Crosby, Alexander E

2016-04-01

To describe the National Violent Death Reporting System (NVDRS). This is a surveillance system for monitoring the occurrence of homicides, suicides, unintentional firearm deaths, deaths of undetermined intent, and deaths from legal intervention (excluding legal executions) in the US. This report provides information about the history, scope, data variables, processes, utility, limitations, and future directions of the NVDRS. The NVDRS currently operates in 32 states, with the goal of future expansion to all 50 states, the District of Columbia, and US territories. The system uses existing primary data sources (death certificates, coroner/medical examiner reports, and law enforcement reports), and links them together to provide a comprehensive picture of the circumstances surrounding violent deaths. This report provides an overview of the NVDRS including a description of the system, discussion of its expanded capability, the use of new technologies as the system has evolved, how the data are being used for violence prevention efforts, and future directions. 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/

Assessment of the wish to hasten death in patients with advanced disease: A systematic review of measurement instruments.

PubMed

Bellido-Pérez, Mercedes; Monforte-Royo, Cristina; Tomás-Sábado, Joaquín; Porta-Sales, Josep; Balaguer, Albert

2017-06-01

Patients with advanced conditions may present a wish to hasten death. Assessing this wish is complex due to the nature of the phenomenon and the difficulty of conceptualising it. To identify and analyse existing instruments for assessing the wish to hasten death and to rate their reported psychometric properties. Systematic review based on PRISMA guidelines. The COnsensus-based Standards for the selection of health Measurement INstruments checklist was used to evaluate the methodological quality of validation studies and the measurement properties of the instrument described. The CINAHL, PsycINFO, Pubmed and Web of Science databases were searched from inception to November 2015. A total of 50 articles involving assessment of the wish to hasten death were included. Eight concerned instrument validation and were evaluated using COnsensus-based Standards for the selection of health Measurement INstruments criteria. They reported data for between two and seven measurement properties, with ratings between fair and excellent. Of the seven instruments identified, the Desire for Death Rating Scale or the Schedule of Attitudes toward Hastened Death feature in 48 of the 50 articles. The Schedule of Attitudes toward Hastened Death is the most widely used and is the instrument whose psychometric properties have been most often analysed. Versions of the Schedule of Attitudes toward Hastened Death are available in five languages other than the original English. This systematic review has analysed existing instruments for assessing the wish to hasten death. It has also explored the methodological quality of studies that have examined the measurement properties of these instruments and offers ratings of the reported properties. These results will be useful to clinicians and researchers with an interest in a phenomenon of considerable relevance to advanced patients.

Assessment of the wish to hasten death in patients with advanced disease: A systematic review of measurement instruments

PubMed Central

Bellido-Pérez, Mercedes; Monforte-Royo, Cristina; Tomás-Sábado, Joaquín; Porta-Sales, Josep; Balaguer, Albert

2016-01-01

Background: Patients with advanced conditions may present a wish to hasten death. Assessing this wish is complex due to the nature of the phenomenon and the difficulty of conceptualising it. Aim: To identify and analyse existing instruments for assessing the wish to hasten death and to rate their reported psychometric properties. Design: Systematic review based on PRISMA guidelines. The COnsensus-based Standards for the selection of health Measurement INstruments checklist was used to evaluate the methodological quality of validation studies and the measurement properties of the instrument described. Data sources: The CINAHL, PsycINFO, Pubmed and Web of Science databases were searched from inception to November 2015. Results: A total of 50 articles involving assessment of the wish to hasten death were included. Eight concerned instrument validation and were evaluated using COnsensus-based Standards for the selection of health Measurement INstruments criteria. They reported data for between two and seven measurement properties, with ratings between fair and excellent. Of the seven instruments identified, the Desire for Death Rating Scale or the Schedule of Attitudes toward Hastened Death feature in 48 of the 50 articles. The Schedule of Attitudes toward Hastened Death is the most widely used and is the instrument whose psychometric properties have been most often analysed. Versions of the Schedule of Attitudes toward Hastened Death are available in five languages other than the original English. Conclusion: This systematic review has analysed existing instruments for assessing the wish to hasten death. It has also explored the methodological quality of studies that have examined the measurement properties of these instruments and offers ratings of the reported properties. These results will be useful to clinicians and researchers with an interest in a phenomenon of considerable relevance to advanced patients. PMID:28124578

Increased reduction in exsanguination rates leaves brain injury as the only major cause of death in blunt trauma.

PubMed

Jochems, D; Leenen, L P H; Hietbrink, F; Houwert, R M; van Wessem, K J P

2018-05-23

Central nervous system (CNS) related injuries and exsanguination have been the most common causes of death in trauma for decades. Despite improvements in haemorrhage control in recent years exsanguination is still a major cause of death. We conducted a prospective database study to investigate the current incidence of haemorrhage related mortality. A prospective database study of all trauma patients admitted to an urban major trauma centre between January 2007 and December 2016 was conducted. All in-hospital trauma deaths were included. Cause of death was reviewed by a panel of trauma surgeons. Patients who were dead on arrival were excluded. Trends in demographics and outcome were analysed per year. Further, 2 time periods (2007-2012 and 2013-2016) were selected representing periods before and after implementation of haemostatic resuscitation and damage control procedures in our hospital to analyse cause of death into detail. 11,553 trauma patients were admitted, 596 patients (5.2%) died. Mean age of deceased patients was 61 years and 61% were male. Mechanism of injury (MOI) was blunt in 98% of cases. Mean ISS was 28 with head injury the most predominant injury (mean AIS head 3.4). There was no statistically significant difference in sex and MOI over time. Even though deceased patients were older in 2016 compared to 2007 (67 vs. 46 years, p < 0.001), mortality was lower in later years (p = 0.02). CNS related injury was the main cause of death in the whole decade; 58% of patients died of CNS in 2007-2012 compared to 76% of patients in 2013-2016 (p = 0.001). In 2007-2012 9% died of exsanguination compared to 3% in 2013-2016 (p = 0.001). In this cohort in a major trauma centre death by exsanguination has decreased to 3% of trauma deaths. The proportion of traumatic brain injury has increased over time and has become the most common cause of death in blunt trauma. Besides on-going prevention of brain injury future studies should focus on treatment strategies preventing secondary damage of the brain once the injury has occurred. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hepatic artery infusion therapy is effective for chemotherapy-resistant liver metastatic colorectal cancer.

PubMed

Goi, Takanori; Naruse, Takayuki; Kimura, Youhei; Fujimoto, Daisuke; Morikawa, Mitsuhiro; Koneri, Kenji; Yamaguchi, Akio

2015-10-09

Systemic FOLFOX (folinic acid (leucovorin (LV)), 5-fluorouracil (5-FU), and oxaliplatin), FOLFIRI (LV, 5-FU, and irinotecan), or FOLFOXIRI (5-FU, leucovorin, oxaliplatin, and irinotecan) chemotherapy regimens and additional molecular-target treatments, including anti-vascular endothelial growth factor, anti-epidermal growth factor receptor, and anti-multi-kinase antibodies, have been recommended for unresectable recurrent colorectal cancers. However, no effective treatments are currently available for cases refractory to these therapies. Therefore, the development of alternative therapies is desired. In the present study, we administered and observed the effectiveness of hepatic artery infusion therapy (HAIC) in patients with unresectable liver metastatic colorectal cancers refractory to systemic chemotherapy. In addition, we observed that in an experimental system with anticancer drug-resistant colorectal cancer lines, apoptosis and cell death could be induced by increasing anticancer drug concentrations. The subjects had liver metastatic colorectal cancers that were unresponsive to systemic chemotherapy (FOLFOX/FOLFIRI) or to additional molecular-target therapies for progressive disease. Hepatic infusion tube placement was conducted according to the Seldinger method to insert a catheter with a side hole via the right femoral artery. A coiling procedure was performed to prevent drug influx into the gastroduodenal artery. Ten subjects were selected, and the results were evaluated after HAIC (5-FU and LV administered once weekly). Moreover, anticancer drug-resistant colorectal cancer lines were subsequently prepared to investigate whether increased anticancer drug concentrations could induce apoptosis or cell death. Of the 10 subjects, 3 (30 %) showed partial response and 4 (40 %) showed no change according to computed tomography imaging findings obtained after hepatic artery infusion. The disease control rate was 70 %. Eight subjects had improved quality of life. Survival time ranged from 2 to 16 months (median, 9 months). Meanwhile, we found that higher anticancer drug concentrations induced apoptosis and cell death in an anticancer drug-resistant colorectal cancer cell line. HAIC was effective in some systemic chemotherapy-resistant colorectal cancers with liver metastases and should be considered as an effective palliative therapy. This supports the finding that apoptosis and cell death could be induced in anticancer drug-resistant colorectal cancer cells in a drug concentration-dependent manner.

Causes and prevention of sudden cardiac death in the elderly.

PubMed

Tung, Patricia; Albert, Christine M

2013-03-01

Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

Conditions 10 years after sudden oak death suppression treatments in Humboldt County, California

Treesearch

Yana Valachovic; Richard Cobb; Brendan Twieg

2017-01-01

In 2006, three isolated sudden oak death- (SOD) infested locations within Humboldt County were selected for silvicultural treatments that targeted the removal and/or reduction of tanoak (Notholithocarpus densiflorus Hook. & Arn.) and California bay laurel (Umbellularia californica Hook. & Arn), the main hosts...

Verbal autopsy in health policy and systems: a literature review

PubMed Central

Balabanova, Dina

2018-01-01

Introduction Estimates suggest that one in two deaths go unrecorded globally every year in terms of medical causes, with the majority occurring in low and middle-income countries (LMICs). This can be related to low investment in civil registration and vital statistics (CRVS) systems. Verbal autopsy (VA) is a method that enables identification of cause of death where no other routine systems are in place and where many people die at home. Considering the utility of VA as a pragmatic, interim solution to the lack of functional CRVS, this review aimed to examine the use of VA to inform health policy and systems improvements. Methods A literature review was conducted including papers published between 2010 and 2017 according to a systematic search strategy. Inclusion of papers and data extraction were assessed by three reviewers. Thereafter, thematic analysis and narrative synthesis were conducted in which evidence was critically examined and key themes were identified. Results Twenty-six papers applying VA to inform health policy and systems developments were selected, including studies in 15 LMICs in Africa, Asia, the Middle East and South America. The majority of studies applied VA in surveillance sites or programmes actively engaging with decision makers and governments in different ways and to different degrees. In the papers reviewed, the value of continuous collection of cause of death data, supplemented by social and community-based investigations and underpinned by electronic data innovations, to establish a robust and reliable evidence base for health policies and programmes was clearly recognised. Conclusion VA has considerable potential to inform policy, planning and measurement of progress towards goals and targets. Working collaboratively at sub-national, national and international levels facilitates data collection, aggregation and dissemination linked to routine information systems. When used in partnerships between researchers and authorities, VA can help to close critical information gaps and guide policy development, implementation, evaluation and investment in health systems. PMID:29736271

Verbal autopsy in health policy and systems: a literature review.

PubMed

Thomas, Lisa-Marie; D'Ambruoso, Lucia; Balabanova, Dina

2018-01-01

Estimates suggest that one in two deaths go unrecorded globally every year in terms of medical causes, with the majority occurring in low and middle-income countries (LMICs). This can be related to low investment in civil registration and vital statistics (CRVS) systems. Verbal autopsy (VA) is a method that enables identification of cause of death where no other routine systems are in place and where many people die at home. Considering the utility of VA as a pragmatic, interim solution to the lack of functional CRVS, this review aimed to examine the use of VA to inform health policy and systems improvements. A literature review was conducted including papers published between 2010 and 2017 according to a systematic search strategy. Inclusion of papers and data extraction were assessed by three reviewers. Thereafter, thematic analysis and narrative synthesis were conducted in which evidence was critically examined and key themes were identified. Twenty-six papers applying VA to inform health policy and systems developments were selected, including studies in 15 LMICs in Africa, Asia, the Middle East and South America. The majority of studies applied VA in surveillance sites or programmes actively engaging with decision makers and governments in different ways and to different degrees. In the papers reviewed, the value of continuous collection of cause of death data, supplemented by social and community-based investigations and underpinned by electronic data innovations, to establish a robust and reliable evidence base for health policies and programmes was clearly recognised. VA has considerable potential to inform policy, planning and measurement of progress towards goals and targets. Working collaboratively at sub-national, national and international levels facilitates data collection, aggregation and dissemination linked to routine information systems. When used in partnerships between researchers and authorities, VA can help to close critical information gaps and guide policy development, implementation, evaluation and investment in health systems.

Surveillance for violent deaths--National Violent Death Reporting System, 16 states, 2009.

PubMed

Karch, Debra L; Logan, Joseph; McDaniel, Dawn; Parks, Sharyn; Patel, Nimesh

2012-09-14

An estimated 50,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2009. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2009. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, and law enforcement reports. NVDRS data collection began in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in 2005, and two (Ohio and Michigan) in 2010, for a total of 19 states. This report includes data from 16 states that collected statewide data in 2009. California is excluded because data were collected in only four counties. Ohio and Michigan are excluded because data collection did not begin until 2010. For 2009, a total of 15,981 fatal incidents involving 16,418 deaths were captured by NVDRS in the 16 states included in this report. The majority (60.6%) of deaths were suicides, followed by homicides and deaths involving legal intervention (i.e., deaths caused by police and other persons with legal authority to use deadly force, excluding legal executions) (24.7%), deaths of undetermined intent (14.2%), and unintentional firearm deaths (0.5%). Suicides occurred at higher rates among males, non-Hispanic whites, American Indians/Alaska Natives, and persons aged 45-54 years. Suicides occurred most often in a house or apartment and involved the use of firearms. Suicides were preceded primarily by mental health, intimate partner, or physical health problems or by a crisis during the previous 2 weeks. Homicides occurred at higher rates among males and persons aged 20-24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm and occurred in a house or apartment or on a street/highway. Homicides were preceded primarily by arguments and interpersonal conflicts or in conjunction with another crime. Characteristics associated with other manners of death, circumstances preceding death, and special populations also are highlighted in this report. This report provides a detailed summary of data from NVDRS for 2009. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected adults aged <55 years, males, and certain racial/ethnic minority populations. For homicides and suicides, relationship problems, interpersonal conflicts, mental health problems, and recent crises were among the primary factors that might have precipitated the fatal injuries. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal costs of violence. Additional efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

Surveillance for violent deaths--national violent death reporting system, 16 States, 2006.

PubMed

Karch, Debra L; Dahlberg, Linda L; Patel, Nimesh; Davis, Terry W; Logan, Joseph E; Hill, Holly A; Ortega, Lavonne

2009-03-20

An estimated 50,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2006. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2006. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, and law enforcement reports. NVDRS began operation in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004 and four (California, Kentucky, New Mexico, and Utah) in 2005, for a total of 17 states. This report includes data from 16 states that collected statewide data; data from California are not included in this report because NVDRS has been implemented only in a limited number of California cities and counties rather than statewide. For 2006, a total of 15,007 fatal incidents involving 15,395 violent deaths occurred in the 16 NVDRS states included in this report. The majority (55.9%) of deaths were suicides, followed by homicides and deaths involving legal intervention (e.g. a suspect is killed by a law enforcement officer in the line of duty)(28.2%), violent deaths of undetermined intent (15.1%), and unintentional firearm deaths (0.7%). Suicides occurred at higher rates among males, American Indians/Alaska Natives (AI/ANs), non-Hispanic whites, and persons aged 45--54 years and occurred most often in a house or apartment and involved the use of firearms. Suicides were precipitated primarily by mental-health, intimate-partner, or physical-health problems or by a crisis during the preceding 2 weeks. Homicides occurred at higher rates among males and persons aged 20--24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm and occurred in a house or apartment or on a street/highway. Homicides were precipitated primarily by arguments and interpersonal conflicts or in conjunction with another crime. Other manners of death and special situations or populations also are highlighted in this report. This report provides a detailed summary of data concerning violent deaths collected by NVDRS for 2006. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence affected adults aged 20--54 years, males, and certain minority populations disproportionately. For many types of violent death, relationship problems, interpersonal conflicts, mental-health problems, and recent crises were among the primary precipitating factors. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to track the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal costs of violence. Further efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

[Death causes in 428 alcoholic patients: a descriptive study].

PubMed

Martínez Lanz, P; Días Coto, C

1992-12-01

Several studies have demonstrated either a direct or an indirect relationship between alcoholism and death causes. The present paper is a descriptive study about death causes in 428 alcoholic patients from San José, Costa Rica, metropolitan area, whose death occurred between 1978 and 1988. Sample subjects were males, under 90-year-old at death time. It was found out that basic death causes were: Traumatism and poisoning, 25%; circulatory system illnesses, 20%; digestive system illnesses, 18.5%, and tumors, 15%.

Cause-specific mortality among children and young adults with epilepsy: Results from the U.S. National Child Death Review Case Reporting System.

PubMed

Tian, Niu; Shaw, Esther C; Zack, Matthew; Kobau, Rosemarie; Dykstra, Heather; Covington, Theresa M

2015-04-01

We investigated causes of death in children and young adults with epilepsy by using data from the U.S. National Child Death Review Case Reporting System (NCDR-CRS), a passive surveillance system composed of comprehensive information related to deaths reviewed by local child death review teams. Information on a total of 48,697 deaths in children and young adults 28days to 24years of age, including 551 deaths with epilepsy and 48,146 deaths without epilepsy, was collected from 2004 through 2012 in 32 states. In a proportionate mortality analysis by official manner of death, decedents with epilepsy had a significantly higher percentage of natural deaths but significantly lower percentages of deaths due to accidents, homicide, and undetermined causes compared with persons without epilepsy. With respect to underlying causes of death, decedents with epilepsy had significantly higher percentages of deaths due to drowning and most medical conditions including pneumonia and congenital anomalies but lower percentages of deaths due to asphyxia, weapon use, and unknown causes compared with decedents without epilepsy. The increased percentages of deaths due to pneumonia and drowning in children and young adults with epilepsy suggest preventive interventions including immunization and better instruction and monitoring before or during swimming. State-specific and national population-based mortality studies of children and young adults with epilepsy are recommended. Published by Elsevier Inc.

Cause-specific mortality among children and young adults with epilepsy: Results from the U.S. National Child Death Review Case Reporting System ☆

PubMed Central

Tian, Niu; Shaw, Esther C.; Zack, Matthew; Kobau, Rosemarie; Dykstra, Heather; Covington, Theresa M.

2015-01-01

We investigated causes of death in children and young adults with epilepsy by using data from the U.S. National Child Death Review Case Reporting System (NCDR-CRS), a passive surveillance system composed of comprehensive information related to deaths reviewed by local child death review teams. Information on a total of 48,697 deaths in children and young adults 28 days to 24 years of age, including 551 deaths with epilepsy and 48,146 deaths without epilepsy, was collected from 2004 through 2012 in 32 states. In a proportionate mortality analysis by official manner of death, decedents with epilepsy had a significantly higher percentage of natural deaths but significantly lower percentages of deaths due to accidents, homicide, and undetermined causes compared with persons without epilepsy. With respect to underlying causes of death, decedents with epilepsy had significantly higher percentages of deaths due to drowning and most medical conditions including pneumonia and congenital anomalies but lower percentages of deaths due to asphyxia, weapon use, and unknown causes compared with decedents without epilepsy. The increased percentages of deaths due to pneumonia and drowning in children and young adults with epilepsy suggest preventive interventions including immunization and better instruction and monitoring before or during swimming. State-specific and national population-based mortality studies of children and young adults with epilepsy are recommended. PMID:25794682

Trauma deaths in a mature urban trauma system: is "trimodal" distribution a valid concept?

PubMed

Demetriades, Demetrios; Kimbrell, Brian; Salim, Ali; Velmahos, George; Rhee, Peter; Preston, Christy; Gruzinski, Ginger; Chan, Linda

2005-09-01

Trimodal distribution of trauma deaths, described more than 20 years ago, is still widely taught in the design of trauma systems. The purpose of this study was to examine the applicability of this trimodal distribution in a modern trauma system. A study of trauma registry and emergency medical services records of trauma deaths in the County of Los Angeles was conducted over a 3-year period. The times from injury to death were analyzed according to mechanism of injury and body area (head, chest, abdomen, extremities) with severe trauma (abbreviated injury score [AIS] >/= 4). During the study period there were 4,151 trauma deaths. Penetrating trauma accounted for 50.0% of these deaths. The most commonly injured body area with critical trauma (AIS >/= 4) was the head (32.0%), followed by chest (20.8%), abdomen (11.5%), and extremities (1.8%). Time from injury to death was available in 2,944 of these trauma deaths. Overall, there were two distinct peaks of deaths: the first peak (50.2% of deaths) occurred within the first hour of injury. The second peak occurred 1 to 6 hours after admission (18.3% of deaths). Only 7.6% of deaths were late (>1 week), during the third peak of the classic trimodal distribution. Temporal distribution of deaths in penetrating trauma was very different from blunt trauma and did not follow the classic trimodal distribution. Other significant independent factors associated with time of death were chest AIS and head AIS. Temporal distribution of deaths as a result of severe head trauma did not follow any pattern and did not resemble classic trimodal distribution at all. The classic "trimodal" distribution of deaths does not apply in our trauma system. Temporal distribution of deaths is influenced by the mechanism of injury, age of the patient, and body area with severe trauma. Knowledge of the time of distribution of deaths might help in allocating trauma resources and focusing research effort.

Costs associated with implementation of computer-assisted clinical decision support system for antenatal and delivery care: case study of Kassena-Nankana district of northern Ghana.

PubMed

Dalaba, Maxwell Ayindenaba; Akweongo, Patricia; Williams, John; Saronga, Happiness Pius; Tonchev, Pencho; Sauerborn, Rainer; Mensah, Nathan; Blank, Antje; Kaltschmidt, Jens; Loukanova, Svetla

2014-01-01

This study analyzed cost of implementing computer-assisted Clinical Decision Support System (CDSS) in selected health care centres in Ghana. A descriptive cross sectional study was conducted in the Kassena-Nankana district (KND). CDSS was deployed in selected health centres in KND as an intervention to manage patients attending antenatal clinics and the labour ward. The CDSS users were mainly nurses who were trained. Activities and associated costs involved in the implementation of CDSS (pre-intervention and intervention) were collected for the period between 2009-2013 from the provider perspective. The ingredients approach was used for the cost analysis. Costs were grouped into personnel, trainings, overheads (recurrent costs) and equipment costs (capital cost). We calculated cost without annualizing capital cost to represent financial cost and cost with annualizing capital costs to represent economic cost. Twenty-two trained CDSS users (at least 2 users per health centre) participated in the study. Between April 2012 and March 2013, users managed 5,595 antenatal clients and 872 labour clients using the CDSS. We observed a decrease in the proportion of complications during delivery (pre-intervention 10.74% versus post-intervention 9.64%) and a reduction in the number of maternal deaths (pre-intervention 4 deaths versus post-intervention 1 death). The overall financial cost of CDSS implementation was US$23,316, approximately US$1,060 per CDSS user trained. Of the total cost of implementation, 48% (US$11,272) was pre-intervention cost and intervention cost was 52% (US$12,044). Equipment costs accounted for the largest proportion of financial cost: 34% (US$7,917). When economic cost was considered, total cost of implementation was US$17,128-lower than the financial cost by 26.5%. The study provides useful information in the implementation of CDSS at health facilities to enhance health workers' adherence to practice guidelines and taking accurate decisions to improve maternal health care.

Nivolumab-induced vitiligo in a metastatic melanoma patient: A case report.

PubMed

Edmondson, Lindsay A; Smith, Leticia V; Mallik, Alka

2017-12-01

The programmed-death-1 inhibitors selectively block programmed-death-1 interaction with its receptor, which restores active T-cell response directed at tumor cells, inducing an anti-tumor effect. This nonspecific activation of the immune system can also lead to a wide spectrum of side effects. Nivolumab has been used effectively to prolong survival in patients with metastatic melanoma and is recommended as a category 1 agent for systemic therapy in metastatic or unresectable melanoma per the National Comprehensive Cancer Network guidelines. We present a case of a 64-year-old woman who began nivolumab therapy for metastatic melanoma. After six doses of nivolumab therapy, the patient experienced generalized hypopigmentation on her face, chest, back, arms, and lower extremities. Although vitiligo has been reported in as many as 10.7% of patients undergoing nivolumab therapy in some clinical trials, we believe this is the first case to describe the progression of nivolumab-induced vitiligo in a metastatic melanoma patient. This case provides significant insight into the onset, symptoms, development, and treatment options for patients experiencing vitiligo as a result of nivolumab therapy.

What about the mothers? An analysis of maternal mortality and morbidity in perinatal health surveillance systems in Europe.

PubMed

Bouvier-Colle, M-H; Mohangoo, A D; Gissler, M; Novak-Antolic, Z; Vutuc, C; Szamotulska, K; Zeitlin, J

2012-06-01

To assess capacity to develop routine monitoring of maternal health in the European Union using indicators of maternal mortality and severe morbidity. Analysis of aggregate data from routine statistical systems compiled by the EURO-PERISTAT project and comparison with data from national enquiries. Twenty-five countries in the European Union and Norway. Women giving birth in participating countries in 2003 and 2004. Application of a common collection of data by selecting specific International Classification of Disease codes from the 'Pregnancy, childbirth and the puerperium' chapter. External validity was assessed by reviewing the results of national confidential enquiries and linkage studies. Maternal mortality ratio, with distribution of specific obstetric causes, and severe acute maternal morbidity, which included: eclampsia, surgery and blood transfusion for obstetric haemorrhage, and intensive-care unit admission. In 22 countries that provided data, the maternal mortality ratio was 6.3 per 100,000 live births overall and ranged from 0 to 29.6. Under-ascertainment was evident from comparisons with studies that use enhanced identification of deaths. Furthermore, routine cause of death registration systems in countries with specific systems for audit reported higher maternal mortality ratio than those in countries without audits. For severe acute maternal morbidity, 16 countries provided data about at least one category of morbidity, and only three provided data for all categories. Reported values ranged widely (from 0.2 to 1.6 women with eclampsia per 1000 women giving birth and from 0.2 to 1.0 hysterectomies per 1000 women). Currently available data on maternal mortality and morbidity are insufficient for monitoring trends over time in Europe and for comparison between countries. Confidential enquiries into maternal deaths are recommended. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

What about the mothers? An analysis of maternal mortality and morbidity in perinatal health surveillance systems in Europe

PubMed Central

Bouvier-Colle, M-H; Mohangoo, AD; Gissler, M; Novak-Antolic, Z; Vutuc, C; Szamotulska, K; Zeitlin, J

2012-01-01

Objective To assess capacity to develop routine monitoring of maternal health in the European Union using indicators of maternal mortality and severe morbidity. Design Analysis of aggregate data from routine statistical systems compiled by the EURO-PERISTAT project and comparison with data from national enquiries. Setting Twenty-five countries in the European Union and Norway. Population Women giving birth in participating countries in 2003 and 2004. Methods Application of a common collection of data by selecting specific International Classification of Disease codes from the ‘Pregnancy, childbirth and the puerperium’ chapter. External validity was assessed by reviewing the results of national confidential enquiries and linkage studies. Main outcome measures Maternal mortality ratio, with distribution of specific obstetric causes, and severe acute maternal morbidity, which included: eclampsia, surgery and blood transfusion for obstetric haemorrhage, and intensive-care unit admission. Results In 22 countries that provided data, the maternal mortality ratio was 6.3 per 100 000 live births overall and ranged from 0 to 29.6. Under-ascertainment was evident from comparisons with studies that use enhanced identification of deaths. Furthermore, routine cause of death registration systems in countries with specific systems for audit reported higher maternal mortality ratio than those in countries without audits. For severe acute maternal morbidity, 16 countries provided data about at least one category of morbidity, and only three provided data for all categories. Reported values ranged widely (from 0.2 to 1.6 women with eclampsia per 1000 women giving birth and from 0.2 to 1.0 hysterectomies per 1000 women). Conclusions Currently available data on maternal mortality and morbidity are insufficient for monitoring trends over time in Europe and for comparison between countries. Confidential enquiries into maternal deaths are recommended. PMID:22571748

Mortality Amenable to Health Care in European Union Countries and Its Limitations.

PubMed

Jarčuška, Peter; Janičko, Martin; Barták, Miroslav; Gavurová, Beáta; Vagašová, Tatiana

2017-12-01

The concept of amenable mortality is intended to assess health care system performance. It is defined as "premature deaths that should not occur in the presence of timely and effective health care". The purpose of paper is to analyse differences in amenable mortality across European Union countries and to determine the associations between amenable mortality and life expectancy at birth. This is a cross-country and time trend analysis. Data on deaths by cause, and five-year age groups were obtained from the World Health Organization database for the 20 European Union countries, throughout the period from 2002 to 2013. The rates of amenable mortality were expressed by the age-standardised death rates per 100,000 inhabitants. We applied the method of direct standardisation using the European Standard Population. Throughout the explored period, the statistically significant variations of the age-standardised death rates in a relation to the European Union average fluctuated from 78.7 per 100,000 inhabitants (95% CI 72.4-84.9) in France to 374.3 per 100,000 inhabitants (95% CI 350.8-397.7) in Latvia. The leading causes of amenable mortality were ischaemic heart disease, cerebrovascular diseases, and colorectal cancer that accounted for, respectively, 42.2%, 19.5%, and 11.3% of overall amenable mortality. As expected, statistically significant strong negative relationship (R 2 =0.95; ρ=-0.98) between amenable mortality and life expectancy at birth was proved by linear regression. The concept has several limitations relating to the selection of causes of death and setting age threshold over time, not consideration actually available health care resources in each country, as well as differences in the prevalence of diseases among countries. We found an explicit divide in amenable mortality rates between more developed countries of Western, Northern and Southern Europe, and less developed countries of Central and Eastern Europe. Increasing of amenable mortality may suggest deterioration in health care system performance. Copyright© by the National Institute of Public Health, Prague 2017.

The Contributions of Selected Diseases to Disparities in Death Rates and Years of Life Lost for Racial/Ethnic Minorities in the United States, 1999–2010

PubMed Central

Peace, Frederick; Howard, Virginia J.

2014-01-01

Introduction Differences in risk for death from diseases and other causes among racial/ethnic groups likely contributed to the limited improvement in the state of health in the United States in the last few decades. The objective of this study was to identify causes of death that are the largest contributors to health disparities among racial/ethnic groups. Methods Using data from WONDER system, we measured the relative (age-adjusted mortality ratio [AAMR]) and absolute (difference in years of life lost [dYLL]) differences in mortality risk between the non-Hispanic white population and the black, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander populations for the 25 leading causes of death. Results Many causes contributed to disparities between non-Hispanic whites and blacks, led by assault (AAMR, 7.56; dYLL, 4.5 million). Malignant neoplasms were the second largest absolute contributor (dYLL, 3.8 million) to black–white disparities; we also found substantial relative and absolute differences for several cardiovascular diseases. Only assault, diabetes, and diseases of the liver contributed substantially to disparities between non-Hispanic whites and Hispanics (AAMR ≥ 1.65; dYLL ≥ 325,000). Many causes of death, led by assault (AAMR, 3.25; dYLL, 98,000), contributed to disparities between non-Hispanic whites and American Indians/Alaska Natives; Asian/Pacific Islanders did not have a higher risk than non-Hispanic whites for death from any disease. Conclusion Assault was a substantial contributor to disparities in mortality among non-Asian racial/ethnic minority populations. Research and intervention resources need to target diseases (such as diabetes and diseases of the liver) that affect certain racial/ethnic populations. PMID:25078566

Understanding the Death of a Child: A Selected Bibliography for Use by Parents, Children, and Professionals.

ERIC Educational Resources Information Center

Miller, James H.; Litton, Freddie W.

1981-01-01

Presents three annotated bibliographies of reading materials to help involved individuals deal with the grief accompanying the death of a child. They include 10 books for parents, 8 for children and adolescents, and 13 books and journals for professionals. (RAA)

Activation of ERK signaling and induction of colon cancer cell death by piperlongumine

USDA-ARS?s Scientific Manuscript database

Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objectiv...

Infant Mortality: Development of a Proposed Update to the Dollfus Classification of Infant Deaths

PubMed Central

Dove, Melanie S.; Minnal, Archana; Damesyn, Mark; Curtis, Michael P.

2015-01-01

Objective Identifying infant deaths with common underlying causes and potential intervention points is critical to infant mortality surveillance and the development of prevention strategies. We constructed an International Classification of Diseases 10th Revision (ICD-10) parallel to the Dollfus cause-of-death classification scheme first published in 1990, which organized infant deaths by etiology and their amenability to prevention efforts. Methods Infant death records for 1996, dual-coded to the ICD Ninth Revision (ICD-9) and ICD-10, were obtained from the CDC public-use multiple-cause-of-death file on comparability between ICD-9 and ICD-10. We used the underlying cause of death to group 27,821 infant deaths into the nine categories of the ICD-9-based update to Dollfus' original coding scheme, published by Sowards in 1999. Comparability ratios were computed to measure concordance between ICD versions. Results The Dollfus classification system updated with ICD-10 codes had limited agreement with the 1999 modified classification system. Although prematurity, congenital malformations, Sudden Infant Death Syndrome, and obstetric conditions were the first through fourth most common causes of infant death under both systems, most comparability ratios were significantly different from one system to the other. Conclusion The Dollfus classification system can be adapted for use with ICD-10 codes to create a comprehensive, etiology-based profile of infant deaths. The potential benefits of using Dollfus logic to guide perinatal mortality reduction strategies, particularly to maternal and child health programs and other initiatives focused on improving infant health, warrant further examination of this method's use in perinatal mortality surveillance. PMID:26556935

Melanoma-Targeted Chemothermotherapy and In Situ Peptide Immunotherapy through HSP Production by Using Melanogenesis Substrate, NPrCAP, and Magnetite Nanoparticles

PubMed Central

Jimbow, Kowichi; Ishii-Osai, Yasue; Ito, Shosuke; Tamura, Yasuaki; Ito, Akira; Yoneta, Akihiro; Kamiya, Takafumi; Yamashita, Toshiharu; Honda, Hiroyuki; Wakamatsu, Kazumasa; Murase, Katsutoshi; Nohara, Satoshi; Nakayama, Eiichi; Hasegawa, Takeo; Yamamoto, Itsuo; Kobayashi, Takeshi

2013-01-01

Exploitation of biological properties unique to cancer cells may provide a novel approach to overcome difficult challenges to the treatment of advanced melanoma. In order to develop melanoma-targeted chemothermoimmunotherapy, a melanogenesis substrate, N-propionyl-4-S-cysteaminylphenol (NPrCAP), sulfur-amine analogue of tyrosine, was conjugated with magnetite nanoparticles. NPrCAP was exploited from melanogenesis substrates, which are expected to be selectively incorporated into melanoma cells and produce highly reactive free radicals through reacting with tyrosinase, resulting in chemotherapeutic and immunotherapeutic effects by oxidative stress and apoptotic cell death. Magnetite nanoparticles were conjugated with NPrCAP to introduce thermotherapeutic and immunotherapeutic effects through nonapoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). During these therapeutic processes, NPrCAP was also expected to provide melanoma-targeted drug delivery system. PMID:23533767

[Thrombotic Microangiopathies].

PubMed

Schubert, Jörg; Dechant, Michael

2018-06-01

Thrombotic microangiopathies are almost devastating diseases leading to death at high frequency if untreated. They consist of at least five distinct entities, TTP, HUS, aHUS, TMA due to drug interference, systemic disease or post therapy TMA. Around 10 years ago there was only one established therapeutic approach as plasmapheresis. Meanwhile, there are new drugs been licensed or within licensing process. Patients with atypical HUS can be treated successfully by the Complement inhibitor Eculizumab. In addition, there is a new inhibitor of von-Willebrand-Polymerisation available. Caplacizumab provides a significantly better remission and decrease in TMA-related death. For therapy associated TMA as VOD/SOS Defibrotide could be established within a phase III study to significantly improve outcomes. In order to select these new medical approaches individual diagnostic parameters need to be established in order to rapidly distinguish between the TMA entities and start targeted therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Cultural imperatives and the ethics of verbal autopsies in rural Ghana

PubMed Central

Aborigo, Raymond A.; Allotey, Pascale; Tindana, Paulina; Azongo, Daniel; Debpuur, Cornelius

2013-01-01

Background Due to a paucity of statistics from vital registration systems in developing countries, the verbal autopsy (VA) approach has been used to obtain cause-specific mortality data by interviewing lay respondents on the signs and symptoms experienced by the deceased prior to death. In societies where the culture of mourning is adhered to, the use of VA could clash with traditional norms, thus warranting ethical consideration by researchers. Objective The study was designed to explore the ethics and cultural context of collecting VA information through a demographic and health surveillance system in the Kassena-Nankana District (KND) of Ghana. Study Design Data were collected through qualitative in-depth interviews (IDIs) with four field staff involved in the routine conduct of VAs, four physicians who code VAs, 20 selected respondents to the VA tool, and eight opinion leaders in the KND. The interviews were supplemented with observation by the researchers and with the field notes of field workers. Interviews were audio-recorded, and local language versions transcribed into English. Thematic analysis was performed using QSR NVivo 8 software. Results The data indicate that cultural sensitivities in VA procedures at both the individual and family levels need greater consideration not only for ethical reasons but also to ensure the quality of the data. Discussions of some deaths are culturally prohibited and therefore lead to refusal of interviews. Families were also concerned about the confidentiality of information because of the potential of blame for the death. VA teams do not necessarily engage in culturally appropriate bereavement practices such as the presentation of tokens. The desire by families for feedback on the cause of death, which is currently not provided by researchers, was frequently expressed. Finally, no standard exists on the culturally acceptable time interval between death and VA interviews. Conclusion Ethical issues need to be given greater consideration in the collection of cause of death data, and this can be achieved through the establishment of processes that allow active engagement with communities, authorities of civil registrations, and Institutional Review Boards to take greater account of local contexts. PMID:24054087

A paradigm for viewing biologic systems as scale-free networks based on energy efficiency: implications for present therapies and the future of evolution.

PubMed

Yun, Anthony J; Lee, Patrick Y; Doux, John D

2006-01-01

A network constitutes an abstract description of the relationships among entities, respectively termed links and nodes. If a power law describes the probability distribution of the number of links per node, the network is said to be scale-free. Scale-free networks feature link clustering around certain hubs based on preferential attachments that emerge due either to merit or legacy. Biologic systems ranging from sub-atomic to ecosystems represent scale-free networks in which energy efficiency forms the basis of preferential attachments. This paradigm engenders a novel scale-free network theory of evolution based on energy efficiency. As environmental flux induces fitness dislocations and compels a new meritocracy, new merit-based hubs emerge, previously merit-based hubs become legacy hubs, and network recalibration occurs to achieve system optimization. To date, Darwinian evolution, characterized by innovation sampling, variation, and selection through filtered termination, has enabled biologic progress through optimization of energy efficiency. However, as humans remodel their environment, increasing the level of unanticipated fitness dislocations and inducing evolutionary stress, the tendency of networks to exhibit inertia and retain legacy hubs engender maladaptations. Many modern diseases may fundamentally derive from these evolutionary displacements. Death itself may constitute a programmed adaptation, terminating individuals who represent legacy hubs and recalibrating the network. As memes replace genes as the basis of innovation, death itself has become a legacy hub. Post-Darwinian evolution may favor indefinite persistence to optimize energy efficiency. We describe strategies to reprogram or decommission legacy hubs that participate in human disease and death.

Development and validation of risk models to select ever-smokers for CT lung-cancer screening

PubMed Central

Katki, Hormuzd A.; Kovalchik, Stephanie A.; Berg, Christine D.; Cheung, Li C.; Chaturvedi, Anil K.

2016-01-01

Importance The US Preventive Services Task Force (USPSTF) recommends computed-tomography (CT) lung-cancer screening for ever-smokers ages 55-80 years who smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung-cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Objective Comparison of modeled outcomes from risk-based CT lung-screening strategies versus USPSTF recommendations. Design/Setting/Participants Empirical risk models for lung-cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age, education, sex, race, smoking intensity/duration/quit-years, Body Mass Index, family history of lung-cancer, and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the US. Models applied to US ever-smokers ages 50-80 (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung-screening, assuming screening for all ever-smokers yields the percent changes in lung-cancer detection and death observed in the NLST. Exposure Annual CT lung-screening for 3 years. Main Outcomes and Measures Model validity: calibration (number of model-predicted cases divided by number of observed cases (Estimated/Observed)) and discrimination (Area-Under-Curve (AUC)). Modeled screening outcomes: estimated number of screen-avertable lung-cancer deaths, estimated screening effectiveness (number needed to screen (NNS) to prevent 1 lung-cancer death). Results Lung-cancer incidence and death risk models were well-calibrated in PLCO and NLST. The lung-cancer death model calibrated and discriminated well for US ever-smokers ages 50-80 (NHIS 1997-2001: Estimated/Observed=0.94, 95%CI=0.84-1.05; AUC=0.78, 95%CI=0.76-0.80). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung-cancer screening and 46,488 (95%CI=43,924-49,053) lung-cancer deaths were estimated as screen-avertable over 5 years (estimated NNS=194, 95%CI=187-201). In contrast, risk-based selection screening the same number of ever-smokers (9.0 million) at highest 5-year lung-cancer risk (≥1.9%), was estimated to avert 20% more deaths (55,717; 95%CI=53,033-58,400) and was estimated to reduce the estimated NNS by 17% (NNS=162, 95%CI=157-166). Conclusions and Relevance Among a cohort of US ever-smokers age 50-80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung-cancer deaths prevented over 5 years along with a lower NNS to prevent 1 lung-cancer death. PMID:27179989

Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening.

PubMed

Katki, Hormuzd A; Kovalchik, Stephanie A; Berg, Christine D; Cheung, Li C; Chaturvedi, Anil K

2016-06-07

The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations. Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations. Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST. Annual CT lung screening for 3 years beginning at age 50 years. For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death). Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]). Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.

Autopsies of sudden infant death syndrome--classification and epidemiology.

PubMed

Hatton, F; Bouvier-Colle, M H; Barois, A; Imbert, M C; Leroyer, A; Bouvier, S; Jougla, E

1995-12-01

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.

Anterior wrist and medial malleolus as the novel sites of tissue selection: a retrospective study on electric shock death through the hand-to-foot circuit pathway.

PubMed

Xu, Guangtao; Su, Ruibing; Lv, Junyao; Hu, Bo; Gu, Huan; Li, Xianxian; Gu, Jiang; Yu, Xiaojun

2017-05-01

Our previous work demonstrated that characteristic changes could occur in the anterior wrist and medial malleolus in electric deaths through the hand-to-foot electric circuit pathway in an electric shock rat model. However, whether the same phenomenon occurs in humans is unknown. The aim of the present retrospective study was to ascertain whether the anterior wrist and medial malleolus could also be selected as the promising and significant sites in electric death through the hand-to-foot circuit pathway. Nineteen human cases from the autopsy and one clinical survivor who sustained a severe electric shock through the hand-to-foot circuit pathway were analyzed. Additional ten autopsy patients who died from traffic accidents and sudden cardiac attacks were used as the control group. Histopathological changes in the soft tissues of the anterior wrist and medial malleolus in all autopsy patients, as well as the electric current pathway of the survivor, were observed. The results showed that the nuclear polarizations in the anterior wrist and medial malleolus soft tissues of the electric death were extremely noticeable as compared with the controls. The most severe electrical injury in the survivor occurred in the anterior wrist. These findings suggest that the soft tissues of the anterior wrist and/or the medial malleolus as the narrowest parts of the limbs could be used as the complementary sites for tissue selection and considered as necessary locations for examinations to assess the electric death in medicolegal identification.

Metabolic and respiratory derangements associated with death in cold-stunned Kemp's ridley turtles (Lepidochelys kempii): 32 cases (2005-2009).

PubMed

Keller, Krista A; Innis, Charles J; Tlusty, Michael F; Kennedy, Adam E; Bean, Sarah B; Cavin, Julie M; Merigo, Constance

2012-02-01

To assess selected clinicopathologic variables at hospital admission (day 1) for cold-stunned Kemp's ridley turtles (Lepidochelys kempii) that died during the first 3 days after admission (nonsurvivors) and turtles that survived (survivors) and to determine the percentage change of each variable from day 1 to day of death (nonsurvivors) or to day 2 or 3 of hospitalization (survivors). Retrospective case-control study. Animals-64 stranded, cold-stunned Kemp's ridley turtles hospitalized from October 2005 through December 2009. Blood gas, pH, Hct, and selected biochemical values in blood samples determined on day 1 and day of death (nonsurvivors; n = 32) or day 2 or 3 of hospitalization (survivors; 32) were obtained from medical records. For each variable, initial values and percentage changes (from initial values to values at the day of death or day 2 or 3 of hospitalization) were compared between survivors and nonsurvivors. Compared with blood analysis findings for survivors, nonsurvivors initially had significantly higher potassium concentration and Pco(2) and significantly lower Po(2), pH, and bicarbonate concentration than did survivors. For the first 2 or 3 days of hospitalization, percentage changes in potassium, lactate, and ionized calcium concentrations were significantly higher and percentage changes in pH and plasma glucose and bicarbonate concentrations were significantly lower in nonsurvivors. At hospital admission, cold-stunned Kemp's ridley turtles were affected by metabolic and respiratory derangements; severe derangements were associated with death. Evaluation of blood gas, pH, Hct, and selected clinicopathologic variables provided useful clinical and prognostic information during rehabilitation of cold-stunned Kemp's ridley turtles.

A screen for immunity genes evolving under positive selection in Drosophila.

PubMed

Jiggins, F M; Kim, K W

2007-05-01

Genes involved in the immune system tend to have higher rates of adaptive evolution than other genes in the genome, probably because they are coevolving with pathogens. We have screened a sample of Drosophila genes to identify those evolving under positive selection. First, we identified rapidly evolving immunity genes by comparing 140 loci in Drosophila erecta and D. yakuba. Secondly, we resequenced 23 of the fastest evolving genes from the independent species pair D. melanogaster and D. simulans, and identified those under positive selection using a McDonald-Kreitman test. There was strong evidence of adaptive evolution in two serine proteases (persephone and spirit) and a homolog of the Anopheles serpin SRPN6, and weaker evidence in another serine protease and the death domain protein dFADD. These results add to mounting evidence that immune signalling pathway molecules often evolve rapidly, possibly because they are sites of host-parasite coevolution.

Seeking order amidst chaos: a systematic review of classification systems for causes of stillbirth and neonatal death, 2009-2014.

PubMed

Leisher, Susannah Hopkins; Teoh, Zheyi; Reinebrant, Hanna; Allanson, Emma; Blencowe, Hannah; Erwich, Jan Jaap; Frøen, J Frederik; Gardosi, Jason; Gordijn, Sanne; Gülmezoglu, A Metin; Heazell, Alexander E P; Korteweg, Fleurisca; Lawn, Joy; McClure, Elizabeth M; Pattinson, Robert; Smith, Gordon C S; Tunçalp, Ӧzge; Wojcieszek, Aleena M; Flenady, Vicki

2016-10-05

Each year, about 5.3 million babies die in the perinatal period. Understanding of causes of death is critical for prevention, yet there is no globally acceptable classification system. Instead, many disparate systems have been developed and used. We aimed to identify all systems used or created between 2009 and 2014, with their key features, including extent of alignment with the International Classification of Diseases (ICD) and variation in features by region, to inform the World Health Organization's development of a new global approach to classifying perinatal deaths. A systematic literature review (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and unpublished studies and national reports describing new classification systems or modifications of existing systems for causes of perinatal death, or that used or tested such systems, between 2009 and 2014. Studies reporting ICD use only were excluded. Data were independently double-extracted (except from non-English publications). Subgroup analyses explored variation by extent and region. Eighty-one systems were identified as new, modifications of existing systems, or having been used between 2009 and 2014, with an average of ten systems created/modified each year. Systems had widely varying characteristics: (i) comprehensiveness (40 systems classified both stillbirths and neonatal deaths); (ii) extent of use (systems were created in 28 countries and used in 40; 17 were created for national use; 27 were widely used); (iii) accessibility (three systems available in e-format); (iv) underlying cause of death (64 systems required a single cause of death); (v) reliability (10 systems tested for reliability, with overall Kappa scores ranging from .35-.93); and (vi) ICD alignment (17 systems used ICD codes). Regional databases were not searched, so system numbers may be underestimated. Some non-differential misclassification of systems was possible. The plethora of systems in use, and continuing system development, hamper international efforts to improve understanding of causes of death. Recognition of the features of currently used systems, combined with a better understanding of the drivers of continued system creation, may help the development of a truly effective global system.

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

PubMed

Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

A multilayered approach for the analysis of perinatal mortality using different classification systems.

PubMed

Gordijn, Sanne J; Korteweg, Fleurisca J; Erwich, Jan Jaap H M; Holm, Jozien P; van Diem, Mariet Th; Bergman, Klasien A; Timmer, Albertus

2009-06-01

Many classification systems for perinatal mortality are available, all with their own strengths and weaknesses: none of them has been universally accepted. We present a systematic multilayered approach for the analysis of perinatal mortality based on information related to the moment of death, the conditions associated with death and the underlying cause of death, using a combination of representatives of existing classification systems. We compared the existing classification systems regarding their definition of the perinatal period, level of complexity, inclusion of maternal, foetal and/or placental factors and whether they focus at a clinical or pathological viewpoint. Furthermore, we allocated the classification systems to one of three categories: 'when', 'what' or 'why', dependent on whether the allocation of the individual cases of perinatal mortality is based on the moment of death ('when'), the clinical conditions associated with death ('what'), or the underlying cause of death ('why'). A multilayered approach for the analysis and classification of perinatal mortality is possible by using combinations of existing systems; for example the Wigglesworth or Nordic Baltic ('when'), ReCoDe ('what') and Tulip ('why') classification systems. This approach is useful not only for in depth analysis of perinatal mortality in the developed world but also for analysis of perinatal mortality in the developing countries, where resources to investigate death are often limited.

How the science of injury prevention contributes to advancing home fire safety in the USA: successes and opportunities.

PubMed

Gielen, Andrea C; Frattaroli, Shannon; Pollack, Keshia M; Peek-Asa, Corinne; Yang, Jingzhen G

2018-06-01

In the decades since the landmark report-America Burning-was published in 1973, the number of home fire deaths has shrunk from >5500 per year to 2650 in 2015. This paper: (1) describes how science and practice in injury prevention and fire and life safety contributed to successful interventions, and (2) identifies emerging strategies and future opportunities to prevent home fire-related deaths. The aims are addressed through the lens of population health research, with a focus on the work of selected Centers for Disease Control and Prevention-funded Injury Control Research Centers. Results are organised using the Haddon Matrix and an ecological model. We found evidence to support interventions that address all components of both the matrix and the model, including: reduced ignition propensity cigarettes, stop smoking campaigns, housing codes, residential sprinkler systems, smoke alarms, community risk reduction, school-based educational programmes, and fire and burn response systems. Future reductions are likely to come from enhancing residential sprinkler and smoke alarm technology, and increasing their utilisation; expanding the use of community risk reduction methods; and implementing new technological solutions. Despite the successes, substantial disparities in home fire death rates remain, reflecting underlying social determinants of health. Most of the evidence-supported interventions were focused on changing the policy and community environments to prevent home fires and reduce injury when a fire occurs. Future prevention efforts should give high priority to addressing the continued disparities in home fire deaths. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pharmacologic antagonism of thromboxane A2 receptors by trimetoquinol analogs in vitro and in vivo

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

Shin, Y.; Romstedt, K.J.; Doyle, K.

1991-01-01

Although (-)-(S)-trimetoquinol (1-(3,4,5-trimethoxy-benzyl)- 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; TMQ) is recognized as a potent bronchodilator, (+)-(R)-TMQ is a selective antagonist of human platelet aggregation and serotonin secretion induced by thromboxane A2 (TXA2) agonists. To confirm the pharmacological actions of TMQ analogs, the interaction of the drugs with TXA2 receptors was examined in human platelets and in a mouse sudden death model. The inhibitory potencies of TMQ analogs (pIC50 values) for displacement of (3H)SQ 29,548 binding to platelets showed excellent correlation with the respective pIC50 (-log IC50) values for U46619-induced aggregation (r = 0.99, P less than 0.01) and serotonin secretion (r = 0.99, Pmore » less than 0.01) in human platelet-rich plasma and for whole blood aggregation (r = 0.99, P less than 0.01). In each system, the rank order of inhibitory potencies was rac-iodoTMQ greater than or equal to (+)-(R)-TMQ greater than rac-TMQ much greater than (-)-(S)-TMQ. Antithrombotic effects of TMQ analogs were evaluated in a mouse sudden death model. In vivo antithrombotic potencies of these compounds were consistent with the in vitro potencies as TXA2 receptor antagonists in platelet systems. Administration of rac-iodoTMQ, (+)-(R)-TMQ and rac-TMQ 15 min before the injection of U46619 (800 micrograms/kg, iv) protected mice against U46619-induced sudden death. On the other hand, (-)-(S)-TMQ did not protect animals against death. Protection of U46619-induced cardiopulmonary thrombosis by TMQ analogs was seen at doses of 3-100 mg/kg.« less

Higher perinatal mortality in National Public Health System hospitals in Belo Horizonte, Brazil, 1999: a compositional or contextual effect?

PubMed

Lansky, S; Subramanian, S V; França, E; Kawachi, I

2007-10-01

In Brazil, it was previously reported that in hospital perinatal, neonatal and infant mortality rates are higher for hospitals contracted to the National Public Health System (SUS) compared with non-SUS hospitals. We analyse whether this reflects a compositional effect (selection of patients) or a contextual effect. Population-based cohort study. Belo Horizonte, Brazil, 1999. A total of 36,469 births in 24 hospitals. A multilevel analysis was carried out using information gathered at the individual level on maternal education (used as an indicator of socio-economic status), maternal age, type of pregnancy and delivery, birthweight and sex of the fetus. Perinatal death. Risk factors for perinatal death included male sex (OR = 1.25; 95% CI 1.01-1.55), birthweight of 1500-2500 g (OR = 7.65; 95% CI 5.74-10.20), birthweight of 500-1500 g (OR = 187.54; 95% CI 141.31-248.39), less than 4 years of maternal education (OR = 2.93; 95% CI 1.68-5.10), as well as birth at private-SUS (OR = 2.92; 95% CI 1.87-4.54) or philanthropic-SUS hospitals (OR = 1.81; 95% CI 1.12-2.92). After controlling for individual characteristics, there was still a significant variation in perinatal deaths between hospitals categories. Independent of compositional (or individual) characteristics, hospital factors exert an influence on the risk of perinatal death, primarily hospital category related to SUS. Considering the highest proportion of births in SUS hospitals in Brazil, especially private-SUS hospitals, improving hospital quality of care is an urgent priority for reducing the toll of perinatal and infant mortality, as well as inequalities in these outcomes.

Surveillance for violent deaths--National Violent Death Reporting System, 16 States, 2007.

PubMed

Karch, Debra L; Dahlberg, Linda L; Patel, Nimesh

2010-05-14

An estimated 50,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 states for 2007. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2007. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, and law enforcement reports. NVDRS began operation in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in 2005, and two states (Ohio and Michigan) were funded to begin data collection in 2010, totaling 19 states. This report includes data from 16 states that collected statewide data in 2007. California data are not included in this report because NVDRS data are collected only in a limited number of California cities and counties rather than statewide. Ohio and Michigan are excluded because they did not begin data collection until 2010. For 2007, a total of 15,882 fatal incidents involving 16,319 deaths occurred in the 16 NVDRS states included in this report. The majority (56.6%) of deaths was suicides, followed by homicides and deaths involving legal intervention (i.e., deaths caused by police and other persons with legal authority to use deadly force, excluding legal executions) (28.0%), deaths of undetermined intent (14.7%), and unintentional firearm deaths (0.7%). Suicides occurred at higher rates among males, American Indians/Alaska Natives, non-Hispanic whites, and persons aged 45--54 years. Suicides occurred most often in a house or apartment and involved the use of firearms. Suicides were precipitated primarily by mental-health, intimate-partner, or physical-health problems, or by a crisis during the preceding 2 weeks. Homicides occurred at higher rates among males and persons aged 20--24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm and occurred in a house or apartment or on a street/highway. Homicides were precipitated primarily by arguments and interpersonal conflicts or in conjunction with another crime. Other manners of death and special situations or populations also are highlighted in this report. This report provides a detailed summary of data from NVDRS for 2007. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected adults aged <55 years, males, and certain minority populations. For homicides and suicides, relationship problems, interpersonal conflicts, mental-health problems, and recent crises were among the primary precipitating factors. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal costs of violence. Further efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

The effects of misclassification biases on veteran suicide rate estimates.

PubMed

Huguet, Nathalie; Kaplan, Mark S; McFarland, Bentson H

2014-01-01

We assessed the impact that possible veteran suicide misclassification biases (i.e., inaccuracy in ascertainment of veteran status on the death certificate and misclassification of suicide as other manner of death) have on veteran suicide rate estimates. We obtained suicide mortality data from the 2003-2010 National Violent Death Reporting System and the 2003-2010 Department of Defense Casualty Analysis System. We derived population estimates from the 2003-2010 American Community Survey and 2003-2010 Department of Veterans Affairs data. We computed veteran and nonveteran suicide rates. The results showed that suicide rates were minimally affected by the adjustment for the misclassification of current military personnel suicides as veterans. Moreover, combining suicides and deaths by injury of undetermined intent did not alter the conclusions. The National Violent Death Reporting System is a valid surveillance system for veteran suicide. However, more than half of younger (< 25 years) male and female suicides, labeled as veterans, were likely to have been current military personnel at the time of their death and misclassified on the death certificate.

Suicide Trends Among and Within Urbanization Levels by Sex, Race/Ethnicity, Age Group, and Mechanism of Death — United States, 2001–2015

PubMed Central

Crosby, Alex E.; Jack, Shane P. D.; Haileyesus, Tadesse; Kresnow-Sedacca, Marcie-jo

2017-01-01

Problem/Condition Suicide is a public health problem and one of the top 10 leading causes of death in the United States. Substantial geographic variations in suicide rates exist, with suicides in rural areas occurring at much higher rates than those occurring in more urban areas. Understanding demographic trends and mechanisms of death among and within urbanization levels is important to developing and targeting future prevention efforts. Reporting Period 2001–2015. Description of System Mortality data from the National Vital Statistics System (NVSS) include demographic, geographic, and cause of death information derived from death certificates filed in the 50 states and the District of Columbia. NVSS was used to identify suicide deaths, defined by International Classification of Diseases, 10th Revision (ICD-10) underlying cause of death codes X60–X84, Y87.0, and U03. This report examines annual county level trends in suicide rates during 2001–2015 among and within urbanization levels by select demographics and mechanisms of death. Counties were collapsed into three urbanization levels using the 2006 National Center for Health Statistics classification scheme. Results Suicide rates increased across the three urbanization levels, with higher rates in nonmetropolitan/rural counties than in medium/small or large metropolitan counties. Each urbanization level experienced substantial annual rate changes at different times during the study period. Across urbanization levels, suicide rates were consistently highest for men and non-Hispanic American Indian/Alaska Natives compared with rates for women and other racial/ethnic groups; however, rates were highest for non-Hispanic whites in more metropolitan counties. Trends indicate that suicide rates for non-Hispanic blacks were lowest in nonmetropolitan/rural counties and highest in more urban counties. Increases in suicide rates occurred for all age groups across urbanization levels, with the highest rates for persons aged 35–64 years. For mechanism of death, greater increases in rates of suicide by firearms and hanging/suffocation occurred across all urbanization levels; rates of suicide by firearms in nonmetropolitan/rural counties were almost two times that of rates in larger metropolitan counties. Interpretation Suicide rates in nonmetropolitan/rural counties are consistently higher than suicide rates in metropolitan counties. These trends also are observed by sex, race/ethnicity, age group, and mechanism of death. Public Health Action Interventions to prevent suicides should be ongoing, particularly in rural areas. Comprehensive suicide prevention efforts might include leveraging protective factors and providing innovative prevention strategies that increase access to health care and mental health care in rural communities. In addition, distribution of socioeconomic factors varies in different communities and needs to be better understood in the context of suicide prevention. PMID:28981481

The tumor macroenvironment and systemic regulation of breast cancer progression.

PubMed

Castaño, Zafira; Tracy, Kristin; McAllister, Sandra S

2011-01-01

Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.

Development and validation of a set of six adaptable prognosis prediction (SAP) models based on time-series real-world big data analysis for patients with cancer receiving chemotherapy: A multicenter case crossover study

PubMed Central

Kanai, Masashi; Okamoto, Kazuya; Yamamoto, Yosuke; Yoshioka, Akira; Hiramoto, Shuji; Nozaki, Akira; Nishikawa, Yoshitaka; Yamaguchi, Daisuke; Tomono, Teruko; Nakatsui, Masahiko; Baba, Mika; Morita, Tatsuya; Matsumoto, Shigemi; Kuroda, Tomohiro; Okuno, Yasushi; Muto, Manabu

2017-01-01

Background We aimed to develop an adaptable prognosis prediction model that could be applied at any time point during the treatment course for patients with cancer receiving chemotherapy, by applying time-series real-world big data. Methods Between April 2004 and September 2014, 4,997 patients with cancer who had received systemic chemotherapy were registered in a prospective cohort database at the Kyoto University Hospital. Of these, 2,693 patients with a death record were eligible for inclusion and divided into training (n = 1,341) and test (n = 1,352) cohorts. In total, 3,471,521 laboratory data at 115,738 time points, representing 40 laboratory items [e.g., white blood cell counts and albumin (Alb) levels] that were monitored for 1 year before the death event were applied for constructing prognosis prediction models. All possible prediction models comprising three different items from 40 laboratory items (40C3 = 9,880) were generated in the training cohort, and the model selection was performed in the test cohort. The fitness of the selected models was externally validated in the validation cohort from three independent settings. Results A prognosis prediction model utilizing Alb, lactate dehydrogenase, and neutrophils was selected based on a strong ability to predict death events within 1–6 months and a set of six prediction models corresponding to 1,2, 3, 4, 5, and 6 months was developed. The area under the curve (AUC) ranged from 0.852 for the 1 month model to 0.713 for the 6 month model. External validation supported the performance of these models. Conclusion By applying time-series real-world big data, we successfully developed a set of six adaptable prognosis prediction models for patients with cancer receiving chemotherapy. PMID:28837592

[Estimation on the mortality and disease burden attributed to selected risk factors in Shandong province].

PubMed

Xu, Ai-qiang; Sun, Jian-dong; Lu, Zi-long; Ma, Ji-xiang; Fu, Zhen-tao; Guo, Xiao-lei

2008-10-01

To determine the major health related risk factors and provide evidence for policy-making, using health burden analysis on selected factors among general population from Shandong province. Based on data derived from the Third Death of Cause Sampling Survey in Shandong, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) were calculated according to the GBD methodology. Deaths and DALYs attributed to the selected risk factors were than estimated together with the PAF data from GBD 2001 study. The indirect method was employed to estimate the YLDs. 51.09% of the total deaths and 31.83% of the total DALYs from the Shandong population were resulted from the 19 selected risk factors. High blood pressure, smoking, low fruit and vegetable intake, alcohol consumption, indoor smoke from solid fuels, high cholesterol, urban air pollution, physical inactivity, overweight and obesity and unsafe injections in health care settings were identified as the top 10 risk factors for mortality which together caused 50.21% of the total deaths. Alcohol use, smoking, high blood pressure, low fruit and vegetable intake, indoor smoke from solid fuels, overweight and obesity, high cholesterol, physical inactivity, urban air pollution and iron-deficiency anemia were proved as the top 10 risk factors related to disease burden and were responsible for 29.04% of the total DALYs. Alcohol use, smoking and high blood pressure were determined as the major risk factors which influencing the health of residents in Shandong. The mortality and burden of disease could be reduced significantly if these major factors were effectively under control.

Pathogen colonization of the gastrointestinal microbiome at intensive care unit admission and risk for subsequent death or infection.

PubMed

Freedberg, Daniel E; Zhou, Margaret J; Cohen, Margot E; Annavajhala, Medini K; Khan, Sabrina; Moscoso, Dagmara I; Brooks, Christian; Whittier, Susan; Chong, David H; Uhlemann, Anne-Catrin; Abrams, Julian A

2018-06-23

Loss of colonization resistance within the gastrointestinal microbiome facilitates the expansion of pathogens and has been associated with death and infection in select populations. We tested whether gut microbiome features at the time of intensive care unit (ICU) admission predict death or infection. This was a prospective cohort study of medical ICU adults. Rectal surveillance swabs were performed at admission, selectively cultured for vancomycin-resistant Enterococcus (VRE), and assessed using 16S rRNA gene sequencing. Patients were followed for 30 days for death or culture-proven bacterial infection. Of 301 patients, 123 (41%) developed culture-proven infections and 76 (25%) died. Fecal biodiversity (Shannon index) did not differ based on death or infection (p = 0.49). The presence of specific pathogens at ICU admission was associated with subsequent infection with the same organism for Escherichia coli, Pseudomonas spp., Klebsiella spp., and Clostridium difficile, and VRE at admission was associated with subsequent Enterococcus infection. In a multivariable model adjusting for severity of illness, VRE colonization and Enterococcus domination (≥ 30% 16S reads) were both associated with death or all-cause infection (aHR 1.46, 95% CI 1.06-2.00 and aHR 1.47, 95% CI 1.00-2.19, respectively); among patients without VRE colonization, Enterococcus domination was associated with excess risk of death or infection (aHR 2.13, 95% CI 1.06-4.29). Enterococcus status at ICU admission was associated with risk for death or all-cause infection, and rectal carriage of common ICU pathogens predicted specific infections. The gastrointestinal microbiome may have a role in risk stratification and early diagnosis of ICU infections.

Non-natural manners of death among users of illicit drugs: Substance findings.

PubMed

Delaveris, Gerd Jorunn M; Teige, Brita; Rogde, Sidsel

2014-05-01

The aim of the study was to explore differences and similarities between the various non-natural manners of death (accident, suicide, homicide) regarding toxicological findings in illicit drug users. Medicolegal autopsy reports from the Institute of Forensic Medicine University of Oslo concerning deaths from 2000 to 2009 were investigated. Those aged 20-59 whose manner of death was non-natural and who tested positive for any narcotic drug (morphine/heroin, amphetamines, ecstasy, cannabis, LSD, PCP, and high levels of GHB in addition to methadone and buprenorphine) were selected. All substance findings were registered and categorized (narcotics, ethanol, and medicinal products). Of the 1603 autopsies that met the selection criteria, 1204 were accidental intoxications, 122 accidents other than intoxication, 114 suicides by intoxication, 119 non-intoxication suicides, and 44 victims of homicide. Poly drug use was found in all manners of death. The drug profile as well as the mean number of substances (illicit drugs and medicinal products) varied from 2.9 to 4.6 substances per case, depending on the manner of death. Intoxication suicides had the highest number of substances and a total drug profile similar to accidental intoxications. Non-intoxication suicides had a total drug profile similar to homicide and accidents other than intoxication. The number of substances found per case increased during the decade, mainly due to increased findings of methadone, cannabis, amphetamines, and benzodiazepines. Methadone findings increased much more than buprenorphine. Methadone was found 20 times more often than buprenorphine in accidental intoxication cases. In summary, poly drug findings are common in adults who suffer a non-natural death while using illicit drugs. The different manners of death have some specific characteristics and significant differences regarding drug profile. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Respiratory function after selective respiratory motor neuron death from intrapleural CTB–saporin injections

PubMed Central

Nichols, Nicole L.; Vinit, Stéphane; Bauernschmidt, Lorene; Mitchell, Gordon S.

2015-01-01

Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB–SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3–28 days after intrapleural injections of: 1) CTB–SAP (25 and 50 μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB + SAP). CTB–SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7 days post-25 μg CTB–SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36 ± 7%; intercostal: 56 ± 10% of controls; n = 9; p < 0.05). CTB–SAP caused minimal cell death in other brainstem or spinal cord regions. CTB–SAP: 1) increased CD11b fractional area in the phrenic motor nucleus, indicating microglial activation; 2) decreased breathing during maximal chemoreceptor stimulation; and 3) diminished phrenic motor output in anesthetized rats (7 days post-25 μg, CTB–SAP: 0.3 ± 0.07 V; CTB + SAP: 1.5 ± 0.3; n = 9; p < 0.05). Intrapleural CTB–SAP represents a novel, inducible model of respiratory motor neuron death and provides an opportunity to study compensation for respiratory motor neuron loss. PMID:25476493

Simultaneous homicide-suicide: a case report of double drowning.

PubMed

Melez, İpek Esen; Avşar, Abdullah; Başpınar, Bünyamin; Melez, Deniz Oğuzhan; Şahin, Fatih; Özdeş, Taşkın

2014-09-01

Homicide-suicide is a tragic phenomenon which typically does not result in a criminal charge or trial. However, correct diagnosis and classification of homicide-suicide cases are important to determine the perpetrators and dynamics of each category properly. The deaths in the homicide-suicide acts can be divided into two categories with respect to the number of involved individuals: dyadic deaths and triple or multiple deaths. These two categories can also be divided into two subgroups according to the chronology of the incidents: simultaneous deaths and consecutive deaths. Herein, a simultaneous homicide-suicide case of a father and daughter where both deaths occurred through drowning which was not found in the selected literature review and where the victim was a child is presented. The article aims to clarify the term discrepancies about multiple death cases in the literature and to discuss the pathological and psychosocial characteristics of the simultaneous dyadic death cases. © 2014 American Academy of Forensic Sciences.

Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways

PubMed Central

Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

2016-01-01

Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance. PMID:27564258

The marine cytotoxin portimine is a potent and selective inducer of apoptosis.

PubMed

Cuddihy, Sarah L; Drake, Sarah; Harwood, D Tim; Selwood, Andrew I; McNabb, Paul S; Hampton, Mark B

2016-12-01

Portimine is a recently discovered member of a class of marine micro-algal toxins called cyclic imines. In dramatic contrast to related compounds in this toxin class, portimine has very low acute toxicity to mice but is highly cytotoxic to cultured cells. In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC 50 values of 6 and 2.5 nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death. Jurkat cells overexpressing the anti-apoptotic protein Bcl-2 or Bax/Bak knockout MEFs were completely protected from portimine. This protection was apparent even at high concentrations of portimine, with no evidence of necrotic cell death, indicating that portimine is a selective chemical inducer of apoptosis. Treatment of the Bcl-2-overexpressing cells with both portimine and the Bcl-2 inhibitor ABT-737 proved a powerful combination, causing >90 % death. We conclude that portimine is one of the most potent naturally derived inducers of apoptosis to be discovered, and it displays strong selectivity for the induction of apoptotic pathways.

Risk Factors Analysis and Death Prediction in Some Life-Threatening Ailments Using Chi-Square Case-Based Reasoning (χ2 CBR) Model.

PubMed

Adeniyi, D A; Wei, Z; Yang, Y

2018-01-30

A wealth of data are available within the health care system, however, effective analysis tools for exploring the hidden patterns in these datasets are lacking. To alleviate this limitation, this paper proposes a simple but promising hybrid predictive model by suitably combining the Chi-square distance measurement with case-based reasoning technique. The study presents the realization of an automated risk calculator and death prediction in some life-threatening ailments using Chi-square case-based reasoning (χ 2 CBR) model. The proposed predictive engine is capable of reducing runtime and speeds up execution process through the use of critical χ 2 distribution value. This work also showcases the development of a novel feature selection method referred to as frequent item based rule (FIBR) method. This FIBR method is used for selecting the best feature for the proposed χ 2 CBR model at the preprocessing stage of the predictive procedures. The implementation of the proposed risk calculator is achieved through the use of an in-house developed PHP program experimented with XAMP/Apache HTTP server as hosting server. The process of data acquisition and case-based development is implemented using the MySQL application. Performance comparison between our system, the NBY, the ED-KNN, the ANN, the SVM, the Random Forest and the traditional CBR techniques shows that the quality of predictions produced by our system outperformed the baseline methods studied. The result of our experiment shows that the precision rate and predictive quality of our system in most cases are equal to or greater than 70%. Our result also shows that the proposed system executes faster than the baseline methods studied. Therefore, the proposed risk calculator is capable of providing useful, consistent, faster, accurate and efficient risk level prediction to both the patients and the physicians at any time, online and on a real-time basis.

Live to die another way: modes of programmed cell death and the signals emanating from dying cells

PubMed Central

Fuchs, Yaron; Steller, Hermann

2015-01-01

Preface All life ends in death, but perhaps one of life’s grander ironies is that it also depends on death. Cell-intrinsic suicide pathways, termed programmed cell death (PCD), are crucial for animal development, tissue homeostasis and pathogenesis. Originally, PCD was virtually synonymous with apoptosis, but recently, alternative PCD mechanisms have been reported. Here, we provide an overview of several distinct PCD mechanisms, namely apoptosis, autophagy and necroptosis. In addition, we discuss the complex signals emanating from dying cells, which can either fuel regeneration or instruct additional killing. Further advances in understanding the physiological role of multiple cell death mechanisms and associated signals will be important to selectively manipulate PCD for therapeutic purposes. PMID:25991373

Antidepressant poisoning deaths in New Zealand for 2001.

PubMed

Reith, David; Fountain, John; Tilyard, Murray; McDowell, Rebecca

2003-10-24

To compare the rates of death per volume of drug dispensed for antidepressants in New Zealand. Deaths from antidepressant poisonings were identified from the reports of coronial inquiries for New Zealand in 2001. Prescriptions for antidepressant medications were identified from the PharmHouse database from 1 January 2001 to 31 December 2001. The rates of deaths (95% CI) per prescription, tablet/capsule or defined daily dose were calculated for individual antidepressants and classes of antidepressant. There were 200 poisoning deaths recorded in the database for New Zealand in 2001. Antidepressants were involved in 41 deaths, and death was attributed to an antidepressant in 23 cases. There were 5.52 (95% CI 3.85-7.68) deaths per 100 000 prescriptions for tricyclic antidepressants (TCAs) and 2.51 (1.57-3.79) deaths per 100 000 prescriptions for selective serotonin reuptake inhibitors (SSRIs). There was marked variability in rates of death per volume of drug dispensed between individual antidepressants. SSRIs have lower rates of death per volume of drug dispensed than TCAs and there is also variation in these rates within these classes of drugs. Toxicity in overdose should be considered when prescribing antidepressants.

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

Large fluctuations in anti-coordination games on scale-free graphs

NASA Astrophysics Data System (ADS)

Sabsovich, Daniel; Mobilia, Mauro; Assaf, Michael

2017-05-01

We study the influence of the complex topology of scale-free graphs on the dynamics of anti-coordination games (e.g. snowdrift games). These reference models are characterized by the coexistence (evolutionary stable mixed strategy) of two competing species, say ‘cooperators’ and ‘defectors’, and, in finite systems, by metastability and large-fluctuation-driven fixation. In this work, we use extensive computer simulations and an effective diffusion approximation (in the weak selection limit) to determine under which circumstances, depending on the individual-based update rules, the topology drastically affects the long-time behavior of anti-coordination games. In particular, we compute the variance of the number of cooperators in the metastable state and the mean fixation time when the dynamics is implemented according to the voter model (death-first/birth-second process) and the link dynamics (birth/death or death/birth at random). For the voter update rule, we show that the scale-free topology effectively renormalizes the population size and as a result the statistics of observables depend on the network’s degree distribution. In contrast, such a renormalization does not occur with the link dynamics update rule and we recover the same behavior as on complete graphs.

Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

PubMed Central

Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

2014-01-01

The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

[Prevalence of Down syndrome using certificates of live births and fetal deaths in México 2008-2011].

PubMed

Sierra Romero, María Del Carmen; Navarrete Hernández, Eduardo; Canún Serrano, Sonia; Reyes Pablo, Aldelmo E; Valdés Hernández, Javier

Down syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation with the clinical presentation of a series of well-defined characteristics. Advanced maternal age has been associated with DS. The databases of all the certificates of live births and fetal deaths in Mexico were combined. Codes based on the International Classification of Diseases 10 th Revision (ICD-10) in Chapter XVII "Congenital malformations, deformations and chromosomal abnormalities" were selected. A database of 8,250,375 births during the period 2008-2011 was constructed: 99.2% were live births with 0.8% of fetal deaths and 3,076 cases diagnosed with DS. The importance of this report is to initiate an epidemiological surveillance of newborn cases of DS nationwide and by state using census information systems available in the country since 2008. An increased risk has been observed for having a child with DS since the mother is ≥ 35 years, as has been reported in other studies. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates?

PubMed

Gil-Mohapel, Joana; Brocardo, Patricia S; Christie, Brian R

2014-04-01

Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.

Death spiral or euthanasia? The demise of generous group health insurance coverage.

PubMed

Pauly, Mark V; Mitchell, Olivia S; Zeng, Yuhui

Employers must determine the types of health care plans to offer and also set employee premiums for each plan provided. Depending on the structure of the employee share of premiums across different health insurance plans, the incentives to choose one plan over another are altered. If employees know premiums do not fully reflect the risk differences among workers, such pricing can give rise to a so-called "death spiral" due to adverse selection. This paper uses longitudinal information from a natural experiment in the management of health benefits for a large employer to explore the impact of moving from a fixed-dollar contribution policy to a partially risk-adjusted employer contribution policy. Our results show that implementing a significant risk adjustment had no discernable effect on adverse selection against the most generous indemnity insurance policy. This stands in stark contrast to previous studies, which have tended to estimate large impacts attributed to selection when employers move to a fixed-dollar policy from one with some risk adjustment. Further analysis suggests that previous studies, which appeared to detect plans in the throes of a death spiral, may instead have been reflecting an inexorable movement away from a non-preferred product, one that would have been inefficient for nearly all workers even in the absence of adverse selection.

SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

EPA Science Inventory

The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

The Health of Children--1970: Selected Data From the National Center for Health Statistics.

ERIC Educational Resources Information Center

National Center for Health Statistics (DHEW/PHS), Hyattsville, MD.

In this booklet, charts and graphs present data from four divisions of the National Center for Health Statistics. The divisions represented are those concerned with vital statistics (births, deaths, fetal deaths, marriages and divorces); health interview statistics (information on health and demographic factors related to illness); health…

Similarities and Dissimilarities in Attitudes toward Death in a Population of Older Persons.

ERIC Educational Resources Information Center

Wass, Hannelore; And Others

1978-01-01

The responses of 171 elderly persons selected from three different types of residence communities to an abbreviated form of Shneidman death questionnaire were analyzed. In addition to some expected similarities, significant differences were found. These differences appear related to educational level, type of residence community (rural,urban), and…

Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.

PubMed

Meyer, Armando; Alexandre, Pedro Celso Braga; Chrisman, Juliana de Rezende; Markowitz, Steven B; Koifman, Rosalina Jorge; Koifman, Sergio

2011-03-01

Several studies suggest that agricultural workers are at higher risk to develop and die by certain types of cancer. Esophageal cancer is not commonly listed among these types. However, some recent studies indicated that if there is an association between agricultural working and esophageal cancer, it s more likely to be observed among workers highly exposed to pesticides. In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Cases were individuals from both genders, 30-59 years old, for whom basic cause of death was ascertained as cancer of the esophagus. For each case, one control was randomly selected from all possible controls for which the basic cause of death was ascertained as different from neoplasm and diseases of the digestive system. In addition, controls matched their cases by sex, age, year of death, and state of residence. Crude and adjusted odds ratios were then calculated to estimate the magnitude of the risk. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working. Copyright © 2010 Elsevier GmbH. All rights reserved.

Causes of death among full term stillbirths and early neonatal deaths in the Region of Southern Denmark.

PubMed

Basu, Millie Nguyen; Johnsen, Iben Birgit Gade; Wehberg, Sonja; Sørensen, Rikke Guldberg; Barington, Torben; Nørgård, Bente Mertz

2018-02-23

We examined the causes of death amongst full term stillbirths and early neonatal deaths. Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20-34 years and with a normal body mass index (BMI). Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Surveillance for Violent Deaths —
National Violent Death Reporting System, 18 States, 2014

PubMed Central

Jack, Shane P.D.; Lyons, Bridget H.; Betz, Carter J.; Petrosky, Emiko

2018-01-01

Problem/Condition In 2014, approximately 59,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC’s National Violent Death Reporting System (NVDRS) regarding violent deaths from 18 U.S. states for 2014. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. Reporting Period Covered 2014. Description of System NVDRS collects data from participating states regarding violent deaths. Data are obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, supplemental homicide reports, hospital data, and crime laboratory data). This report includes data from 18 states that collected statewide data for 2014 (Alaska, Colorado, Georgia, Kentucky, Maryland, Massachusetts, Michigan, New Jersey, New Mexico, North Carolina, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin). NVDRS collates documents for each death and links deaths that are related (e.g., multiple homicides, a homicide followed by a suicide, or multiple suicides) into a single incident. Results For 2014, a total of 22,098 fatal incidents involving 22,618 deaths were captured by NVDRS in the 18 states included in this report. The majority of deaths were suicides (65.6%), followed by homicides (22.5%), deaths of undetermined intent (10.0%), deaths involving legal intervention (1.3%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force, excluding legal executions), and unintentional firearm deaths (<1%). The term “legal intervention” is a classification incorporated into the International Classification of Diseases, Tenth Revision (ICD-10) and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement. Suicides occurred at higher rates among males, non-Hispanic American Indian/Alaska Natives (AI/AN), non-Hispanic whites, persons aged 45–54 years, and males aged ≥75 years. Suicides were preceded primarily by a mental health, intimate partner, substance abuse, or physical health problem or a crisis during the previous or upcoming 2 weeks. Homicide rates were higher among males and persons aged <1 year and 15–44 years; rates were highest among non-Hispanic black and AI/AN males. Homicides primarily were precipitated by arguments and interpersonal conflicts, occurrence in conjunction with another crime, or related to intimate partner violence (particularly for females). When the relationship between a homicide victim and a suspected perpetrator was known, it was most often either an acquaintance/friend or an intimate partner. Legal intervention death rates were highest among males and persons aged 20–44 years; rates were highest among non-Hispanic black males and Hispanic males. Precipitating factors for the majority of legal intervention deaths were alleged criminal activity in progress, the victim reportedly using a weapon in the incident, a mental health or substance abuse problem, an argument or conflict, or a recent crisis. Deaths of undetermined intent occurred more frequently among males, particularly non-Hispanic black and AI/AN males, and persons aged 30–54 years. Substance abuse, mental health problems, physical health problems, and a recent crisis were the most common circumstances preceding deaths of undetermined intent. Unintentional firearm deaths were more frequent among males, non-Hispanic whites, and persons aged 10–24 years; these deaths most often occurred while the shooter was playing with a firearm and were most often precipitated by a person unintentionally pulling the trigger or mistakenly thinking the firearm was unloaded. Interpretation This report provides a detailed summary of data from NVDRS for 2014. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected persons aged <65 years, males, and certain minority populations. The primary precipitating factors for homicides and suicides were intimate partner problems, interpersonal conflicts, mental health and substance abuse problems, and recent crises. Public Health Action NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths. For example, North Carolina VDRS data were used to improve case ascertainment of pregnancy-associated suicides, Wisconsin VDRS data were used to develop the statewide suicide prevention strategy, and Colorado VDRS data were used to develop programs and prevention strategies for suicide among veterans. The continued development and expansion of NVDRS to include all U.S. states, territories, and the District of Columbia are essential to public health efforts to reduce the impact of violence. PMID:29389917

Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids.

PubMed

Mercadante, Sebastiano; Intravaia, Giuseppe; Villari, Patrizia; Ferrera, Patrizia; Riina, Salvatore; David, Fabrizio; Mangione, Salvatore

2007-01-01

The aim of this study was to evaluate the clinical response to a combination of intrathecal morphine and levobupivacaine in advanced cancer patients who were highly opioid-tolerant, being previously treated with multiple opioid trials unsuccessfully. Initial intrathecal morphine dose was calculated from the previous opioid consumption using a morphine oral-intrathecal ratio of 100:1. Then, doses of both drugs were modified during the treatment according to the clinical needs and balanced with adverse effects. Fifty-five patients were assessed during admission, before starting the intrathecal treatment, during the titration phase, and followed up to death, by frequent phone contacts or visits, as available. Pain and symptom intensities were recorded before starting the intrathecal treatment (T0), at time of hospital discharge (T dis), and then at 1 month (T1), 3 months (T3), 6 months (T6) intervals, and the last observation, at least 1 week before death (T death). Fifty-five patients were selected for starting an intrathecal treatment. Thirty-two patients were males. The mean age was 60 years (95% CI 57-63), and 65.4% of patients were under 65 years. The most frequent indication was the presence of adverse effects and poor pain control. Complete data with adequate follow-up until death were available in 45 patients. Statistical differences in pain intensity were found at the different time intervals examined until death. Statistical decreases in the intensity of drowsiness and confusion were found until 1 month after starting intrathecal therapy. Statistical differences were found in daily intrathecal morphine doses, with a 3-fold increase at time of hospital discharge. Subsequently, further increases in doses were not significant. Conversely, systemic opioids, expressed as oral morphine equivalents, significantly decreased at all the intervals examined until death. Early complications included mild bleeding in 2 patients, without consequences, headache in 4 patients, bladder catheterization in 6 patients, reoperation for bleeding or changes of catheter position in 4 patients, unrelated death in 1 patient, and stroke in another 1. Late complications included local infection in 2 patients, and discontinuation of intrathecal therapy due to spinal compression. In patients who had received multiple trial of opioids and routes of administration, the intrathecal treatment started with an oral-intrathecal morphine conversion ratio of 100:1, and local anesthetics at the most convenient clinical doses provided a long-term improvement of analgesia, with a decrease in adverse effects and opioid consumption until death.

Rates and correlates of undetermined deaths among African Americans: results from the National Violent Death Reporting System.

PubMed

Huguet, Nathalie; Kaplan, Mark S; McFarland, Bentson H

2012-04-01

Little is known about the factors associated with undetermined death classifications among African Americans. In this study, the rates of undetermined deaths were assessed, the prevalence of missing information was estimated, and whether the circumstances preceding death differ by race were examined. Data were derived from the 2005-2008 National Violent Death Reporting System. African Americans had higher prevalence of missing information than Whites. African Americans classified as undetermined deaths were more likely to be older, women, never married/single, to have had a blood alcohol content at or above the legal limit, and to have had a substance abuse problem. The results suggest that racial differences in the preponderance and the type of evidence surrounding the death may affect death classification. © 2012 The American Association of Suicidology.

Cause of and factors associated with stillbirth: a systematic review of classification systems.

PubMed

Aminu, Mamuda; Bar-Zeev, Sarah; van den Broek, Nynke

2017-05-01

An estimated 2.6 million stillbirths occur worldwide each year. A standardized classification system setting out possible cause of death and contributing factors is useful to help obtain comparative data across different settings. We undertook a systematic review of stillbirth classification systems to highlight their strengths and weaknesses for practitioners and policymakers. We conducted a systematic search and review of the literature to identify the classification systems used to aggregate information for stillbirth and perinatal deaths. Narrative synthesis was used to compare the range and depth of information required to apply the systems, and the different categories provided for cause of and factors contributing to stillbirth. A total of 118 documents were screened; 31 classification systems were included, of which six were designed specifically for stillbirth, 14 for perinatal death, three systems included neonatal deaths and two included infant deaths. Most (27/31) were developed in and first tested using data obtained from high-income settings. All systems required information from clinical records. One-third of the classification systems (11/31) included information obtained from histology or autopsy. The percentage where cause of death remained unknown ranged from 0.39% using the Nordic-Baltic classification to 46.4% using the Keeling system. Over time, classification systems have become more complex. The success of application is dependent on the availability of detailed clinical information and laboratory investigations. Systems that adopt a layered approach allow for classification of cause of death to a broad as well as to a more detailed level. © 2017 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

Evaluation of Two Compressed Air Foam Systems for Culling Caged Layer Hens.

PubMed

Benson, Eric R; Weiher, Jaclyn A; Alphin, Robert L; Farnell, Morgan; Hougentogler, Daniel P

2018-04-24

Outbreaks of avian influenza (AI) and other highly contagious poultry diseases continue to be a concern for those involved in the poultry industry. In the situation of an outbreak, emergency depopulation of the birds involved is necessary. In this project, two compressed air foam systems (CAFS) were evaluated for mass emergency depopulation of layer hens in a manure belt equipped cage system. In both experiments, a randomized block design was used with multiple commercial layer hens treated with one of three randomly selected depopulation methods: CAFS, CAFS with CO₂ gas, and CO₂ gas. In Experiment 1, a Rowe manufactured CAFS was used, a selection of birds were instrumented, and the time to unconsciousness, brain death, altered terminal cardiac activity and motion cessation were recorded. CAFS with and without CO₂ was faster to unconsciousness, however, the other parameters were not statistically significant. In Experiment 2, a custom Hale based CAFS was used to evaluate the impact of bird age, a selection of birds were instrumented, and the time to motion cessation was recorded. The difference in time to cessation of movement between pullets and spent hens using CAFS was not statistically significant. Both CAFS depopulate caged layers, however, there was no benefit to including CO₂.

Addressing maternal deaths due to violence: the Illinois experience.

PubMed

Koch, Abigail R; Geller, Stacie E

2017-11-01

Homicide, suicide, and substance abuse accounted for nearly one fourth of all pregnancy-associated deaths in Illinois from 2002 through 2013. Maternal mortality review in Illinois has been primarily focused on obstetric and medical causes and little is known about the circumstances surrounding deaths due to homicide, suicide, and substance abuse, if they are pregnancy related, and if the deaths are potentially preventable. To address this issue, we implemented a process to form a second statewide maternal mortality review committee for deaths due to violence in late 2014. We convened a stakeholder group to accomplish 3 tasks: (1) identify appropriate committee members; (2) identify potential types and sources of information that would be required for a meaningful review of violent maternal deaths; and (3) revise the Maternal Mortality Review Form. Because homicide, suicide, and substance abuse are closely linked to the social determinants of health, the review committee needed to have a broad membership with expertise in areas not required for obstetric maternal mortality review, including social service and community organizations. Identifying additional sources of information is critical; the state Violent Death Reporting System, case management data, and police and autopsy reports provide contextual information that cannot be found in medical records. The stakeholder group revised the Maternal Mortality Review Form to collect information relevant to violent maternal deaths, including screening history and psychosocial history. The form guides the maternal mortality review committee for deaths due to violence to identify potentially preventable factors relating to the woman, her family, systems of care, the community, the legal system, and the institutional environment. The committee has identified potential opportunities to decrease preventable death requiring cooperation with social service agencies and the criminal justice system in addition to the physical and mental health care systems. Illinois has demonstrated that by engaging appropriate members and expanding the information used, it is possible to conduct meaningful reviews of these deaths and make recommendations to prevent future deaths. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.

PubMed

Ogawa, Mikako; Tomita, Yusuke; Nakamura, Yuko; Lee, Min-Jung; Lee, Sunmin; Tomita, Saori; Nagaya, Tadanobu; Sato, Kazuhide; Yamauchi, Toyohiko; Iwai, Hidenao; Kumar, Abhishek; Haystead, Timothy; Shroff, Hari; Choyke, Peter L; Trepel, Jane B; Kobayashi, Hisataka

2017-02-07

Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.

SpxB is a suicide gene of Streptococcus pneumoniae and confers a selective advantage in an in vivo competitive colonization model.

PubMed

Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M; Lipsitch, Marc; Malley, Richard

2007-09-01

The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H(2)O(2)), not LytA, and that the gene responsible for H(2)O(2) production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H(2)O(2) in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing DeltaspxB mutants that do not produce H(2)O(2). Likewise, addition of H(2)O(2) to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While DeltalytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H(2)O(2) has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the DeltaspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization.

SpxB Is a Suicide Gene of Streptococcus pneumoniae and Confers a Selective Advantage in an In Vivo Competitive Colonization Model▿

PubMed Central

Regev-Yochay, Gili; Trzcinski, Krzysztof; Thompson, Claudette M.; Lipsitch, Marc; Malley, Richard

2007-01-01

The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H2O2), not LytA, and that the gene responsible for H2O2 production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H2O2 in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing ΔspxB mutants that do not produce H2O2. Likewise, addition of H2O2 to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While ΔlytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H2O2 has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the ΔspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization. PMID:17631628

Selective serotonin reuptake inhibitors and adverse pregnancy outcomes.

PubMed

Wen, Shi Wu; Yang, Qiuying; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Nimrod, Carl; Walker, Mark

2006-04-01

The purpose of this study was to assess the safety of the use of selective serotonin reuptake inhibitors in pregnancy. We carried out a retrospective cohort study of 972 pregnant women who had been given at least 1 selective serotonin reuptake inhibitor prescription in the year before delivery and 3878 pregnant women who did not receive selective serotonin reuptake inhibitors and who were matched by the year of the infant's birth, the type of institute at birth, and the mother's postal code from 1990 to 2000 in the Canadian province of Saskatchewan. The risks of low birth weight (adjusted odds ratio, 1.58; 95% CI, 1.19, 2.11), preterm birth (adjusted odds ratio, 1.57; 95% CI, 1.28, 1.92), fetal death (adjusted odds ratio, 2.23; 95% CI, 1.01, 4.93), and seizures (adjusted odds ratio, 3.87; 95% CI, 1.00, 14.99) were increased in infants who were born to mothers who had received selective serotonin reuptake inhibitor therapy. The use of selective serotonin reuptake inhibitors in pregnancy may increase the risks of low birth weight, preterm birth, fetal death, and seizures.

Obesity-related mortality in France, Italy, and the United States: a comparison using multiple cause-of-death analysis

PubMed Central

Barbieri, Magali; Egidi, Viviana; Demuru, Elena; Frova, Luisa; Meslé, France; Pappagallo, Marilena

2018-01-01

Objectives We investigate the reporting of obesity on death certificates in three countries (France, Italy, and the United States) with different levels of prevalence, and we examine which causes are frequently associated with obesity. Methods We use cause-of-death data for all deaths at ages 50–89 in 2010–2011. Since obesity may not be the underlying cause (UC) of death, we compute age- and sex- standardized death rates considering all mentions of obesity (multiple causes or MC). We use cluster analyses to identify patterns of cause-of-death combinations. Results Obesity is selected as UC in no more than 20% of the deaths with a mention of obesity. Mortality levels, whether measured from the UC or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death combinations are similar across the countries. In addition to strong links with cardiovascular diseases and diabetes, we identify several less familiar associations. Conclusions Considering all mentions on the deaths certificates reduces the underestimation of obesity-related mortality based on the UC only. It also enables us to describe the various mortality patterns involving obesity. PMID:28497238

Obesity-related mortality in France, Italy, and the United States: a comparison using multiple cause-of-death analysis.

PubMed

Barbieri, Magali; Désesquelles, Aline; Egidi, Viviana; Demuru, Elena; Frova, Luisa; Meslé, France; Pappagallo, Marilena

2017-07-01

We investigate the reporting of obesity on death certificates in three countries (France, Italy, and the United States) with different levels of prevalence, and we examine which causes are frequently associated with obesity. We use cause-of-death data for all deaths at ages 50-89 in 2010-2011. Since obesity may not be the underlying cause (UC) of death, we compute age- and sex-standardized death rates considering all mentions of obesity (multiple causes or MC). We use cluster analyses to identify patterns of cause-of-death combinations. Obesity is selected as UC in no more than 20% of the deaths with a mention of obesity. Mortality levels, whether measured from the UC or the MC, are weakly related to levels of prevalence. Patterns of cause-of-death combinations are similar across the countries. In addition to strong links with cardiovascular diseases and diabetes, we identify several less familiar associations. Considering all mentions on the deaths certificates reduces the underestimation of obesity-related mortality based on the UC only. It also enables us to describe the various mortality patterns involving obesity.

Variability of undetermined manner of death classification in the US.

PubMed

Breiding, M J; Wiersema, B

2006-12-01

To better understand variations in classification of deaths of undetermined intent among states in the National Violent Death Reporting System (NVDRS). Data from the NVDRS and the National Vital Statistics System were used to compare differences among states. Percentages of deaths assigned undetermined intent, rates of deaths of undetermined intent, rates of fatal poisonings broken down by cause of death, composition of poison types within the undetermined-intent classification. Three states within NVDRS (Maryland, Massachusetts, and Rhode Island) evidenced increased numbers of deaths of undetermined intent. These same states exhibited high rates of undetermined death and, more specifically, high rates of undetermined poisoning deaths. Further, these three states evidenced correspondingly lower rates of unintentional poisonings. The types of undetermined poisonings present in these states, but not present in other states, are typically the result of a combination of recreational drugs, alcohol, or prescription drugs. The differing classification among states of many poisoning deaths has implications for the analysis of undetermined deaths within the NVDRS and for the examination of possible/probable suicides contained within the undetermined- or accidental-intent classifications. The NVDRS does not collect information on unintentional poisonings, so in most states data are not collected on these possible/probable suicides. The authors believe this is an opportunity missed to understand the full range of self-harm deaths in the greater detail provided by the NVDRS system. They advocate a broader interpretation of suicide to include the full continuum of deaths resulting from self-harm.

Attitude Toward Death in Healthy People and Patients With Diabetes and Cancer

PubMed Central

Nozari, Masoumeh; Dousti, Yarali

2013-01-01

Background A person's beliefs can influence the progression of his/her disease;and battling an illness can trigger severe anxiety about death. This study aims to compare the attitude toward death between healthy people and those suffering from diabetes and cancer. Methods In a cross-sectional study, 300 individuals were selected by convenient sampling method. Three groups were matched by gender, age, education, and monthly income. Information was collected through a Death Attitude Profile-Revised (DAPR) questionnaire and Analyzed Via Covariance (ANCOVA). Results The results indicated no difference in death attitude among the three groups (f=2.705, p<0.05). All the three groups displayed a higher mean in neutral and approach acceptance. Conclusion In this study, it was found that disease did not seem to change death attitudes; rather the patients' current attitude had been shaped by previous stages of their sickness. PMID:25250117

Geographic variation in inquest rates in Australia.

PubMed

Walter, Simon J; Bugeja, Lyndal; Spittal, Matthew J; Studdert, David M

2012-11-01

This paper examines the relationship between the remoteness of locations in which deaths occur and coroners' decisions to hold inquests. We analysed 16,242 deaths investigated by coroners in three Australian states over 7.5 yrs. We used a choropleth map to show inquest rates in each remoteness locality (excluding deaths for which inquests were mandated by statute). We then used adjusted logistic regression to assess the association between the remoteness of a death's location and the odds coroners would select it for investigation by inquest. We found the remoteness of a death's location strongly and positively predicts the chance that an inquest will be held. Like analogous findings in the delivery of health services, this small-area variation in legal decision making raises questions of appropriateness. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

PubMed

O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

2011-12-01

When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

Development of an antibiotic marker-free platform for heterologous protein production in Streptomyces.

PubMed

Sevillano, Laura; Díaz, Margarita; Santamaría, Ramón I

2017-09-26

The industrial use of enzymes produced by microorganisms is continuously growing due to the need for sustainable solutions. Nevertheless, many of the plasmids used for recombinant production of proteins in bacteria are based on the use of antibiotic resistance genes as selection markers. The safety concerns and legal requirements surrounding the increased use of antibiotic resistance genes have made the development of new antibiotic-free approaches essential. In this work, a system completely free of antibiotic resistance genes and useful for the production of high yields of proteins in Streptomyces is described. This system is based on the separation of the two components of the yefM/yoeBsl (antitoxin/toxin) operon; the toxin (yoeBsl) gene, responsible for host death, is integrated into the genome and the antitoxin gene (yefMsl), which inactivates the toxin, is located in the expression plasmid. To develop this system, the toxin gene was integrated into the genome of a strain lacking the complete operon, and the antibiotic resistance gene integrated along with the toxin was eliminated by Cre recombinase to generate a final host strain free of any antibiotic resistance marker. In the same way, the antibiotic resistance gene from the final expression plasmid was removed by Dre recombinase. The usefulness of this system was analysed by checking the production of two hydrolases from different Streptomyces. Production of both proteins, with potential industrial use, was high and stable over time after strain storage and after serial subcultures. These results support the robustness and stability of the positive selection system developed. The total absence of antibiotic resistance genes makes this system a powerful tool for using Streptomyces as a host to produce proteins at the industrial level. This work is the first Streptomyces antibiotic marker-free system to be described. Graphical abstract Antibiotic marker-free platform for protein expression in Streptomyces. The antitoxin gene present in the expression plasmid counteracts the effect of the toxin gene in the genome. In absence of the expression plasmid, the toxin causes cell death ensuring that only plasmid-containing cells persist.

Using CRISPR-Cas systems as antimicrobials.

PubMed

Bikard, David; Barrangou, Rodolphe

2017-06-01

Although CRISPR-Cas systems naturally evolved to provide adaptive immunity in bacteria and archaea, Cas nucleases can be co-opted to target chromosomal sequences rather than invasive genetic elements. Although genome editing is the primary outcome of self-targeting using CRISPR-based technologies in eukaryotes, self-targeting by CRISPR is typically lethal in bacteria. Here, we discuss how DNA damage introduced by Cas nucleases in bacteria can efficiently and specifically lead to plasmid curing or drive cell death. Specifically, we discuss how various CRISPR-Cas systems can be engineered and delivered using phages or phagemids as vectors. These principles establish CRISPR-Cas systems as potent and programmable antimicrobials, and open new avenues for the development of CRISPR-based tools for selective removal of bacterial pathogens and precise microbiome composition alteration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reasons for not reporting deaths: a qualitative study in rural Vietnam.

PubMed

Huy, Tran Quang; Johansson, Annika; Long, Nguyen Hoang

2007-01-01

This qualitative study explores socio-cultural and health systems factors that may impact on death reporting by lay people to registry systems at the commune level. Information on local perceptions of death and factors influencing death reporting were gathered through nine focus group discussions with people of different religions and ethnic affiliations in a rural district of northern Vietnam. Participants classified deaths as "elderly deaths," "young deaths," and "child deaths." Child deaths, including newborn deaths, used to be considered punishment for sins committed by ancestors, but this is no longer the case. Concepts of the human soul and afterlife differ between the Catholic and Buddhist groups, influencing funeral rituals and reporting, especially of infant deaths. Participants regarded elderly deaths as "natural" and "deserved," while young deaths were seen as either "good deaths" or "bad deaths." "Bad deaths" were defined as deaths of "dishonourable" persons who had led a "bad life" involving activities such as gambling, drinking or stealing. The causes of "bad deaths" and deaths due to stigmatized diseases (e.g., HIV/AIDS, tuberculosis and leprosy) were often concealed by the family. The study suggests that the risk of under-reporting deaths seems to be largest for deaths of infants and "bad deaths." Little awareness of regulations and lack of incentives for reporting or lack of sanctions for not reporting deaths also result in under-reporting of deaths. Therefore, education programs and enforcement of legal regulations on death notification should be emphasized. The risk of misreporting the real causes of "bad deaths" and deaths due to stigmatized diseases should be considered in verbal autopsy interviews. Using different sources of information (triangulation) is useful in order to minimize both under-registration and misreporting causes of death.

Secondary metabolites in fungus-plant interactions

PubMed Central

Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

2015-01-01

Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

A Differential Evolution-Based Routing Algorithm for Environmental Monitoring Wireless Sensor Networks

PubMed Central

Li, Xiaofang; Xu, Lizhong; Wang, Huibin; Song, Jie; Yang, Simon X.

2010-01-01

The traditional Low Energy Adaptive Cluster Hierarchy (LEACH) routing protocol is a clustering-based protocol. The uneven selection of cluster heads results in premature death of cluster heads and premature blind nodes inside the clusters, thus reducing the overall lifetime of the network. With a full consideration of information on energy and distance distribution of neighboring nodes inside the clusters, this paper proposes a new routing algorithm based on differential evolution (DE) to improve the LEACH routing protocol. To meet the requirements of monitoring applications in outdoor environments such as the meteorological, hydrological and wetland ecological environments, the proposed algorithm uses the simple and fast search features of DE to optimize the multi-objective selection of cluster heads and prevent blind nodes for improved energy efficiency and system stability. Simulation results show that the proposed new LEACH routing algorithm has better performance, effectively extends the working lifetime of the system, and improves the quality of the wireless sensor networks. PMID:22219670

Impact of documentation errors on accuracy of cause of death coding in an educational hospital in Southern Iran.

PubMed

Haghighi, Mohammad Hosein Hayavi; Dehghani, Mohammad; Teshnizi, Saeid Hoseini; Mahmoodi, Hamid

2014-01-01

Accurate cause of death coding leads to organised and usable death information but there are some factors that influence documentation on death certificates and therefore affect the coding. We reviewed the role of documentation errors on the accuracy of death coding at Shahid Mohammadi Hospital (SMH), Bandar Abbas, Iran. We studied the death certificates of all deceased patients in SMH from October 2010 to March 2011. Researchers determined and coded the underlying cause of death on the death certificates according to the guidelines issued by the World Health Organization in Volume 2 of the International Statistical Classification of Diseases and Health Related Problems-10th revision (ICD-10). Necessary ICD coding rules (such as the General Principle, Rules 1-3, the modification rules and other instructions about death coding) were applied to select the underlying cause of death on each certificate. Demographic details and documentation errors were then extracted. Data were analysed with descriptive statistics and chi square tests. The accuracy rate of causes of death coding was 51.7%, demonstrating a statistically significant relationship (p=.001) with major errors but not such a relationship with minor errors. Factors that result in poor quality of Cause of Death coding in SMH are lack of coder training, documentation errors and the undesirable structure of death certificates.

The Role of Mitophagy in Innate Immunity

PubMed Central

Gkikas, Ilias; Palikaras, Konstantinos; Tavernarakis, Nektarios

2018-01-01

Mitochondria are cellular organelles essential for multiple biological processes, including energy production, metabolites biosynthesis, cell death, and immunological responses among others. Recent advances in the field of immunology research reveal the pivotal role of energy metabolism in innate immune cells fate and function. Therefore, the maintenance of mitochondrial network integrity and activity is a prerequisite for immune system homeostasis. Mitochondrial selective autophagy, known as mitophagy, surveils mitochondrial population eliminating superfluous and/or impaired organelles and mediating cellular survival and viability in response to injury/trauma and infection. Defective removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and development of inflammatory diseases. Here, we review the molecular mechanisms of mitophagy and highlight its critical role in the innate immune system homeostasis.

New approaches for Helicobacter vaccine development--difficulties and progress.

PubMed

Jagusztyn-Krynicka, Elzbieta K; Godlewska, Renata

2008-01-01

Despite the enormous progress in understanding the process of bacterial pathogenesis and interactions of pathogens with eucaryotic cells the infectious diseases still remain the main cause of human premature deaths. It is now recognized that Helicobacter pylori infects about half of the world's population. Based on results of clinical studies the World Health Organization has assigned H. pylori as a class I carcinogen. The review presents new achievements aimed at construction efficient and safe anti-Helicobacter vaccine. We discuss the new global technologies such as immunoproteomics employed for selecting new candidates for vaccine construction as well as new vaccine delivery systems. The review presents also our knowledge concerning H. pylori interaction with immune system which might facilitate modulation of the host immune system by specific adjuvant included into vaccine.

Epidemiological transition in a rural community of northern India: 18-year mortality surveillance using verbal autopsy.

PubMed

Kumar, Rajesh; Kumar, Dinesh; Jagnoor, J; Aggarwal, Arun K; Lakshmi, P V M

2012-10-01

Information on causes of death is vital for planning of health services. However, vital events registration systems are weak in developing countries. Therefore, verbal autopsy (VA) tools were incorporated in a community-based surveillance system to track causes of death. Trained fieldworker identified all deaths and interviewed a living relative of those who had died during 1992-2009, using VA, in eight villages of Haryana (11,864 populations). These field reports detailing events preceding death were reviewed by two trained physicians, who independently assigned an International Classification of Disease-10 code to each death. Discrepancies were resolved through reconciliation and, if necessary, adjudication. Non-communicable conditions were the leading causes of death (47.6%) followed by communicable diseases including maternal, perinatal and nutritional conditions (34.0%), and injuries (11.4%). Cause of death could not be determined in 6.9% cases. Deaths due to cardiovascular diseases showed a significant rise, whereas deaths due to diarrhoeal diseases have declined (p<0.01). Majority (90.0%) of the deceased had contacted a healthcare provider during illness but only 11.5% were admitted in hospital before death. Rising trend of cardiovascular diseases observed in a rural community of Haryana in India calls for reorientation of rural healthcare delivery system for prevention and control of chronic diseases.

The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca2+ signaling.

PubMed

Vervloessem, Tamara; Ivanova, Hristina; Luyten, Tomas; Parys, Jan B; Bultynck, Geert

2017-06-01

Anti-apoptotic B cell-lymphoma-2 (Bcl-2) proteins are emerging as therapeutic targets in a variety of cancers for precision medicines, like the BH3-mimetic drug venetoclax (ABT-199), which antagonizes the hydrophobic cleft of Bcl-2. However, the impact of venetoclax on intracellular Ca 2+ homeostasis and dynamics in cell systems has not been characterized in detail. Here, we show that venetoclax did not affect Ca 2+ -transport systems from the endoplasmic reticulum (ER) in permeabilized cell systems. Venetoclax (1μM) did neither trigger Ca 2+ release by itself nor affect agonist-induced Ca 2+ release in a variety of intact cell models. Among the different cell types, we also studied two Bcl-2-dependent cancer cell models with a varying sensitivity towards venetoclax, namely SU-DHL-4 and OCI-LY-1, both diffuse large B-cell lymphoma cell lines. Acute application of venetoclax did also not dysregulate Ca 2+ signaling in these Bcl-2-dependent cancer cells. Moreover, venetoclax-induced cell death was independent of intracellular Ca 2+ overload, since Ca 2+ buffering using BAPTA-AM did not suppress venetoclax-induced cell death. This study therefore shows that venetoclax does not dysregulate the intracellular Ca 2+ homeostasis in a variety of cell types, which may underlie its limited toxicity in human patients. Furthermore, venetoclax-induced cell death in Bcl-2-dependent cancer cells is not mediated by intracellular Ca 2+ overload. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2016 Elsevier B.V. All rights reserved.

Use of verbal autopsy and social autopsy in humanitarian crises.

PubMed

Thomas, Lisa-Marie; D'Ambruoso, Lucia; Balabanova, Dina

2018-01-01

Two billion people live in countries affected by conflict, violence and fragility. These are exceptional situations in which mortality shifts dramatically and in which civil registration and vital statistics systems are often weakened or cease to function. Verbal autopsy and social autopsy (VA and SA) are methods used to assign causes of death and understand the contexts in which these occur, in settings where information is otherwise unavailable. This review sought to explore the use of VA and SA in humanitarian crises, with a focus on how these approaches are used to inform policy and programme responses. A rapid scoping review was conducted on the use of VA and SA in humanitarian crises in low and middle-income countries since 1991. Drawing on a maximum variation approach, two settings of application ('application contexts') were selected and investigated via nine semi-structured expert interviews. VA can determine causes of death in crisis-affected populations where no other registration system is in place. Combined with SA and active community involvement, these methods can deliver a holistic view of obstacles to seeking and receiving essential healthcare, yielding context-specific information to inform appropriate responses. The contexts in which VA and SA are used require adaptations to standard tools, and new mobile developments in VA raise specific ethical considerations. Furthermore, collecting and sythesising data in a timely, continuous manner, and ensuring coordination and communication between agencies, is important to realise the potential of these approaches. VA and SA are valuable research methods to foster evidence-informed responses for populations affected by humanitarian crises. When coordinated and communicated effectively, data generated through these methods can help to identify levels, causes and circumstances of deaths among vulnerable groups, and can enable planning and allocating resources effectively, potentially improving health system resilience to future crises.

A population-based analysis of injury-related deaths and access to trauma care in rural-remote Northwest British Columbia.

PubMed

Simons, Richard; Brasher, Penelope; Taulu, Tracey; Lakha, Nasira; Molnar, Nadine; Caron, Nadine; Schuurman, Nadine; Evans, David; Hameed, Morad

2010-07-01

Injury rates and injury mortality rates are generally higher in rural and remote communities compared with urban jurisdictions as has been shown to be the case in the rural-remote area of Northwest (NW) British Columbia (BC). The purpose of study was to identify: (1) the place and timing of death following injury in NW BC, (2) access to and quality of local trauma services, and (3) opportunities to improve trauma outcomes. Quantitative data from demographic and geographic databases, the BC Trauma Registry, Hospital discharge abstract database, and the BC Coroner's Office, along with qualitative data from chart reviews of selected major trauma cases, and interviews with front-line trauma care providers were collated and analyzed for patients sustaining injury in NW BC from April 2001 to March 2006. The majority of trauma deaths (82%) in NW BC occur prehospital. Patients arriving alive to NW hospitals have low hospital mortality (1.0%), and patients transferring from NW BC to tertiary centers have better outcomes than matched patients achieving direct entry into the tertiary center by way of geographic proximity. Access to local trauma services was compromised by: incident discovery, limited phone service (land lines/cell), incomplete 911 emergency medical services system access, geographical and climate challenges compounded by limited transportation options, airport capabilities and paramedic training level, dysfunctional hospital no-refusal policies, lack of a hospital destination policies, and lack of system leadership and coordination. Improving trauma outcomes in this rural-remote jurisdiction requires a systems approach to address root causes of delays in access to care, focusing on improved access to emergency medical services, hospital bypass and destination protocols, improved transportation options, advanced life support transfer capability, and designated, coordinated local trauma services.

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

PubMed

Arana, Jorge E; Harrington, Theresa; Cano, Maria; Lewis, Paige; Mba-Jonas, Adamma; Rongxia, Li; Stewart, Brock; Markowitz, Lauri E; Shimabukuro, Tom T

2018-03-20

The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data. Published by Elsevier Ltd.

Hepatocellular carcinoma: From clinical practice to evidence-based treatment protocols

PubMed Central

Galun, Danijel; Basaric, Dragan; Zuvela, Marinko; Bulajic, Predrag; Bogdanovic, Aleksandar; Bidzic, Nemanja; Milicevic, Miroslav

2015-01-01

Hepatocellular carcinoma (HCC) is one of the major malignant diseases in many healthcare systems. The growing number of new cases diagnosed each year is nearly equal to the number of deaths from this cancer. Worldwide, HCC is a leading cause of cancer-related deaths, as it is the fifth most common cancer and the third most important cause of cancer related death in men. Among various risk factors the two are prevailing: viral hepatitis, namely chronic hepatitis C virus is a well-established risk factor contributing to the rising incidence of HCC. The epidemic of obesity and the metabolic syndrome, not only in the United States but also in Asia, tend to become the leading cause of the long-term rise in the HCC incidence. Today, the diagnosis of HCC is established within the national surveillance programs in developed countries while the diagnosis of symptomatic, advanced stage disease still remains the characteristic of underdeveloped countries. Although many different staging systems have been developed and evaluated the Barcelona-Clinic Liver Cancer staging system has emerged as the most useful to guide HCC treatment. Treatment allocation should be decided by a multidisciplinary board involving hepatologists, pathologists, radiologists, liver surgeons and oncologists guided by personalized -based medicine. This approach is important not only to balance between different oncologic treatments strategies but also due to the complexity of the disease (chronic liver disease and the cancer) and due to the large number of potentially efficient therapies. Careful patient selection and a tailored treatment modality for every patient, either potentially curative (surgical treatment and tumor ablation) or palliative (transarterial therapy, radioembolization and medical treatment, i.e., sorafenib) is mandatory to achieve the best treatment outcome. PMID:26380652

Fork head controls the timing and tissue selectivity of steroid-induced developmental cell death

PubMed Central

Cao, Chike; Liu, Yanling; Lehmann, Michael

2007-01-01

Cell death during Drosophila melanogaster metamorphosis is controlled by the steroid hormone 20-hydroxyecdysone (20E). Elements of the signaling pathway that triggers death are known, but it is not known why some tissues, and not others, die in response to a particular hormone pulse. We found that loss of the tissue-specific transcription factor Fork head (Fkh) is both required and sufficient to specify a death response to 20E in the larval salivary glands. Loss of fkh itself is a steroid-controlled event that is mediated by the 20E-induced BR-C gene, and that renders the key death regulators hid and reaper hormone responsive. These results implicate the D. melanogaster FOXA orthologue Fkh with a novel function as a competence factor for steroid-controlled cell death. They explain how a specific tissue is singled out for death, and why this tissue survives earlier hormone pulses. More generally, they suggest that cell identity factors like Fkh play a pivotal role in the normal control of developmental cell death. PMID:17339378

New advances in hepatocellular carcinoma

PubMed Central

Pascual, Sonia; Herrera, Iván; Irurzun, Javier

2016-01-01

Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

Social inequalities in total and cause-specific mortality of a sample of the Italian population, from 1999 to 2007.

PubMed

Marinacci, Chiara; Grippo, Francesco; Pappagallo, Marilena; Sebastiani, Gabriella; Demaria, Moreno; Vittori, Patrizia; Caranci, Nicola; Costa, Giuseppe

2013-08-01

There is extensive documentation on social inequalities in mortality across Europe, showing heterogeneity among countries. Italy contributed to this comparative research, through longitudinal systems from northern or central cities of the country. This study aims to analyse educational inequalities in general and cause-specific mortality in a sample of the Italian population. Study population was selected within a cohort of 123,056 individuals, followed up for mortality through record linkage with national archive of death certificates for the period 1999-2007. People aged between 25 and 74 years were selected (n = 81,763); relative risks of death by education were estimated through Poisson models, stratified according to sex and adjusted for age and geographic area of residence. Heterogeneity of risks by area of residence was evaluated. Men and women with primary education or less show 79% and 63% higher mortality risks, respectively, compared with graduates. Mortality risks seem to frequently increase with decreasing education, with a significant linear trend among men. For men, social inequalities appear related to mortality due to diseases of the circulatory system and to all neoplasms, whereas for women, they are related to inequalities in cancer mortality. Results from the first follow-up of a national sample highlight that Italy presents significant differences in mortality according to the socio-economic conditions of both men and women. These results not only challenge policies aimed at redistributing resources to individuals and groups, but also those policies that direct programmes and resources for treatment and prevention according to the different health needs.

The effect of damping on a quantum system containing a Kerr-like medium

NASA Astrophysics Data System (ADS)

Mohamed, A.-B. A.; Sebawe Abdalla, M.; Obada, A.-S. F.

2018-05-01

An analytical description is given for a model which represents the interaction between Su(1,1) and Su(2) quantum systems taking into account Su(1,1)-cavity damping and Kerr medium properties. The analytic solution for the master equation of the density matrix is obtained. The examination of the effects of the damping parameter as well as the Kerr-like medium features is performed. The atomic inversion is discussed where the revivals and collapses phenomenon is realized at the considered period of time. Our study is extended to include the degree of entanglement where the system shows partial entanglement in all cases, however, disentanglement is also observed. The death and rebirth is seen in the system provided one selects the suitable values of the parameters. The correlation function of the system shows non-classical as well as classical behavior.

5 CFR 843.303 - Marriage duration requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cause of death for criminal or insurance purposes is conclusive evidence of whether a death is accidental. (3) A death certificate showing the cause of death as accident or homicide is prima facie... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and...

Compiling mortality statistics from civil registration systems in Viet Nam: the long road ahead.

PubMed

Rao, Chalapati; Osterberger, Brigitta; Anh, Tran Dam; MacDonald, Malcolm; Chúc, Nguyen Thi Kim; Hill, Peter S

2010-01-01

Accurate mortality statistics, needed for population health assessment, health policy and research, are best derived from data in vital registration systems. However, mortality statistics from vital registration systems are not available for several countries including Viet Nam. We used a mixed methods case study approach to assess vital registration operations in 2006 in three provinces in Viet Nam (Hòa Bình, Thùa Thiên-Hué and Bình Duong), and provide recommendations to strengthen vital registration systems in the country. For each province we developed life tables from population and mortality data compiled by sex and age group. Demographic methods were used to estimate completeness of death registration as an indicator of vital registration performance. Qualitative methods (document review, key informant interviews and focus group discussions) were used to assess administrative, technical and societal aspects of vital registration systems. Completeness of death registration was low in all three provinces. Problems were identified with the legal framework for registration of early neonatal deaths and deaths of temporary residents or migrants. The system does not conform to international standards for reporting cause of death or for recording detailed statistics by age, sex and cause of death. Capacity-building along with an intersectoral coordination committee involving the Ministries of Justice and Health and the General Statistics Office would improve the vital registration system, especially with regard to procedures for death registration. There appears to be strong political support for sentinel surveillance systems to generate reliable mortality statistics in Viet Nam.

Prediction of mesothelioma and lung cancer in a cohort of asbestos exposed workers.

PubMed

Gasparrini, Antonio; Pizzo, Anna Maria; Gorini, Giuseppe; Seniori Costantini, Adele; Silvestri, Stefano; Ciapini, Cesare; Innocenti, Andrea; Berry, Geoffrey

2008-01-01

Several papers have reported state-wide projections of mesothelioma deaths, but few have computed these predictions in selected exposed groups. To predict the future deaths attributable to asbestos in a cohort of railway rolling stock workers. The future mortality of the 1,146 living workers has been computed in term of individual probability of dying for three different risks: baseline mortality, lung cancer excess, mesothelioma mortality. Lung cancer mortality attributable to asbestos was calculated assuming the excess risk as stable or with a decrease after a period of time since first exposure. Mesothelioma mortality was based on cumulative exposure and time since first exposure, with the inclusion of a term for clearance of asbestos fibres from the lung. The most likely range of the number of deaths attributable to asbestos in the period 2005-2050 was 15-30 for excess of lung cancer, and 23-35 for mesothelioma. This study provides predictions of asbestos-related mortality even in a selected cohort of exposed subjects, using previous knowledge about exposure-response relationship. The inclusion of individual information in the projection model helps reduce misclassification and improves the results. The method could be extended in other selected cohorts.

The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases.

PubMed

Siakavellas, Spyros I; Sfikakis, Petros P; Bamias, Giorgos

2015-08-01

TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcium regulates cell death in cancer: Roles of the mitochondria and mitochondria-associated membranes (MAMs).

PubMed

Danese, Alberto; Patergnani, Simone; Bonora, Massimo; Wieckowski, Mariusz R; Previati, Maurizio; Giorgi, Carlotta; Pinton, Paolo

2017-08-01

Until 1972, the term 'apoptosis' was used to differentiate the programmed cell death that naturally occurs in organismal development from the acute tissue death referred to as necrosis. Many studies on cell death and programmed cell death have been published and most are, at least to some degree, related to cancer. Some key proteins and molecular pathways implicated in cell death have been analyzed, whereas others are still being actively researched; therefore, an increasing number of cellular compartments and organelles are being implicated in cell death and cancer. Here, we discuss the mitochondria and subdomains of the endoplasmic reticulum (ER) that interact with mitochondria, the mitochondria-associated membranes (MAMs), which have been identified as critical hubs in the regulation of cell death and tumor growth. MAMs-dependent calcium (Ca 2+ ) release from the ER allows selective Ca 2+ uptake by the mitochondria. The perturbation of Ca 2+ homeostasis in cancer cells is correlated with sustained cell proliferation and the inhibition of cell death through the modulation of Ca 2+ signaling. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

Distinct mortality profile in systemic sclerosis: a death certificate study in Rio de Janeiro, Brazil (2006-2015) using a multiple causes of death analysis.

PubMed

de Rezende, Rodrigo Poubel Vieira; Gismondi, Ronaldo Altenburg; Maleh, Haim Cesar; de Miranda Coelho, Elisa Mendes; Vieira, Carol Sartori; Rosa, Maria Luiza Garcia; Mocarzel, Luis Otavio

2017-12-16

The objective of this study was to assess the mortality profile related to SSc in the state of Rio de Janeiro, Brazil. We retrospectively examined all registered deaths in the region (2006-2015 period) in which the diagnosis of SSc was mentioned on any line of the death certificates (underlying cause of death [UCD], n = 223; non-UCD, n = 151). Besides the analysis of gender, age, and the causes of death, we also compared the mortality from UCDs between individuals whose death causes included SSc (cases) and those whose death causes did not include SSc (deceased controls). For the latter comparison, we used the mortality odds ratio to approximate the cause-specific standardized mortality ratio. We identified 1495 death causes among the 374 SSc cases. The mean age at death of the SSc cases (85% women) was significantly lower than that of the controls (n = 1,294,117) (58.7 vs. 65.5 years, respectively). The main death causes were circulatory system diseases, infections, and respiratory diseases (36%, 34%, and 21% of SSc cases, respectively). Compared to the deceased controls, there were proportionally more deaths among the SSc cases from pulmonary arterial hypertension, lung fibrosis, septicemia, gastrointestinal hemorrhage, other systemic connective tissue diseases, and heart failure (for death age < 50 years). We confirmed the high burden of cardiovascular, respiratory, and infectious causes in this predominantly non-Caucasian sample of SSc patients. Of interest, the percentage of infection-related deaths in our report was about three times higher than that in SSc studies with predominantly Caucasian populations.

Gender and age differences in suicide mortality in the context of violent death: findings from a multi-state population-based surveillance system.

PubMed

Bozzay, Melanie L; Liu, Richard T; Kleiman, Evan M

2014-07-01

Males are more likely than females to die by all forms of violent death, including suicide. The primary purpose of the present study was to explore whether the gender difference in suicide rates is largely accounted for by males' general greater tendency to experience violent deaths. The current study examined gender and age differences in suicides and other violent deaths, using data from a population-based surveillance system. Pearson's chi-square tests and logistic regression analyses were conducted with data for 32,107 decedents in the 2003-2005 National Violent Death Reporting System (NVDRS). Decedents were categorized by gender, age, and death by suicide versus other violent means. When suicides were examined in the greater context of violent death, the total proportion of violent deaths due to suicide did not differ across gender. When deaths were examined by age group, after controlling for ethnicity, marital status, and U.S. location in which the death occurred, males in early to mid childhood were significantly more likely than same-aged females to die by suicide relative to all other violent deaths. The portion of deaths due to suicide was for the most part equal across both genders in late childhood, young adulthood, and mid-adulthood. Older males were more likely than older females to die by suicide relative to other violent deaths. Our findings suggest that that the risk of dying by suicide relative to other violent deaths may be more pronounced at certain developmental stages for each gender. This knowledge may be valuable in tailoring prevention strategies. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute Anticholinesterase Pesticide Poisoning Caused a Long-Term Mortality Increase

PubMed Central

Huang, Hung-Sheng; Hsu, Chien-Chin; Weng, Shih-Feng; Lin, Hung-Jung; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

2015-01-01

Abstract Acute anticholinesterase pesticide (organophosphate and carbamate) poisoning (ACPP) often produces severe complications, and sometimes death. We investigated the long-term mortality of patients with ACPP because it is not sufficiently understood. In this retrospective nationwide population-based cohort study, 818 patients with ACPP and 16,360 healthy comparisons from 1999 to 2010 were selected from Taiwan's National Health Insurance Research Database. They were followed until 2011. Ninety-four (11.5%) ACPP patients and 793 (4.9%) comparisons died (P < 0.01) during follow-up. The incidence rate ratios (IRRs) of death were 2.5 times higher in ACPP patients than in comparisons (P < 0.01). The risk of death was particularly high in the first month after ACPP (IRR: 92.7; 95% confidence interval [CI]: 45.0–191.0) and still high for ∼6 months (IRR: 3.8; 95% CI: 1.9–7.4). After adjusting for age, gender, selected comorbidities, geographic area, and monthly income, the hazard ratio of death for ACPP patients was still 2.4 times higher than for comparisons. Older age (≥35 years), male gender, diabetes mellitus, coronary artery disease, hypertension, stroke, mental disorder, and lower monthly income also predicted death. ACPP significantly increased long-term mortality. In addition to early follow-up after acute treatment, comorbidity control and socioeconomic assistance are needed for patients with ACPP. PMID:26222853

Role of the immune modulator programmed cell death-1 during development and apoptosis of mouse retinal ganglion cells

PubMed Central

Chen, Ling; Sham, Caroline W.; Chan, Ann M.; Francisco, Loise M.; Wu, Yin; Mareninov, Sergey; Sharpe, Arlene H.; Freeman, Gordon J.; Yang, Xian-Jie; Braun, Jonathan; Gordon, Lynn K.

2011-01-01

PURPOSE Mammalian programmed cell death-1 (PD-1) is a membrane-associated receptor regulating the balance between T cell activation, tolerance and immunopathology, however its role in neurons has not yet been defined. We investigate the hypothesis that PD-1 signaling actively promotes retinal ganglion cell (RGC) death within the developing mouse retina. METHODS Mature retinal cell types expressing PD-1 were identified by immunofluorescence staining of vertical retina sections; developmental expression was localized by immunostaining and quantified by Western analysis. PD-1 involvement in developmental RGC survival was assessed in vitro using retina explants and in vivo using PD-1 knockout mice. PD-1 ligand gene expression was detected by RT-PCR. RESULTS PD-1 is expressed in most adult RGCs, and undergoes dynamic upregulation during the early postnatal window of retinal cell maturation and physiological programmed cell death (PCD). In vitro blockade of PD-1 signaling during this time selectively increases survival of RGCs. Furthermore, PD-1 deficient mice show a selective increase in RGC number in the neonatal retina at the peak of developmental RGC death. Lastly, throughout postnatal retina maturation, we find gene expression of both immune PD-1 ligand genes, PD-L1 and PD-L2. CONCLUSIONS These findings collectively support a novel role for a PD-1-mediated signaling pathway in developmental PCD during postnatal RGC maturation. PMID:19420345

Acute Anticholinesterase Pesticide Poisoning Caused a Long-Term Mortality Increase: A Nationwide Population-Based Cohort Study.

PubMed

Huang, Hung-Sheng; Hsu, Chien-Chin; Weng, Shih-Feng; Lin, Hung-Jung; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

2015-07-01

Acute anticholinesterase pesticide (organophosphate and carbamate) poisoning (ACPP) often produces severe complications, and sometimes death. We investigated the long-term mortality of patients with ACPP because it is not sufficiently understood. In this retrospective nationwide population-based cohort study, 818 patients with ACPP and 16,360 healthy comparisons from 1999 to 2010 were selected from Taiwan's National Health Insurance Research Database. They were followed until 2011. Ninety-four (11.5%) ACPP patients and 793 (4.9%) comparisons died (P < 0.01) during follow-up. The incidence rate ratios (IRRs) of death were 2.5 times higher in ACPP patients than in comparisons (P < 0.01). The risk of death was particularly high in the first month after ACPP (IRR: 92.7; 95% confidence interval [CI]: 45.0-191.0) and still high for ~6 months (IRR: 3.8; 95% CI: 1.9-7.4). After adjusting for age, gender, selected comorbidities, geographic area, and monthly income, the hazard ratio of death for ACPP patients was still 2.4 times higher than for comparisons. Older age (≥35 years), male gender, diabetes mellitus, coronary artery disease, hypertension, stroke, mental disorder, and lower monthly income also predicted death. ACPP significantly increased long-term mortality. In addition to early follow-up after acute treatment, comorbidity control and socioeconomic assistance are needed for patients with ACPP.

Modeling decay rates of dead wood in a neotropical forest.

PubMed

Hérault, Bruno; Beauchêne, Jacques; Muller, Félix; Wagner, Fabien; Baraloto, Christopher; Blanc, Lilian; Martin, Jean-Michel

2010-09-01

Variation of dead wood decay rates among tropical trees remains one source of uncertainty in global models of the carbon cycle. Taking advantage of a broad forest plot network surveyed for tree mortality over a 23-year period, we measured the remaining fraction of boles from 367 dead trees from 26 neotropical species widely varying in wood density (0.23-1.24 g cm(-3)) and tree circumference at death time (31.5-272.0 cm). We modeled decay rates within a Bayesian framework assuming a first order differential equation to model the decomposition process and tested for the effects of forest management (selective logging vs. unexploited), of mode of death (standing vs. downed) and of topographical levels (bottomlands vs. hillsides vs. hilltops) on wood decay rates. The general decay model predicts the observed remaining fraction of dead wood (R2 = 60%) with only two biological predictors: tree circumference at death time and wood specific density. Neither selective logging nor local topography had a differential effect on wood decay rates. Including the mode of death into the model revealed that standing dead trees decomposed faster than downed dead trees, but the gain of model accuracy remains rather marginal. Overall, these results suggest that the release of carbon from tropical dead trees to the atmosphere can be simply estimated using tree circumference at death time and wood density.

Classification System for the Sudden Unexpected Infant Death Case Registry and its Application

PubMed Central

Shapiro-Mendoza, Carrie K.; Camperlengo, Lena; Ludvigsen, Rebecca; Cottengim, Carri; Anderson, Robert N.; Andrew, Thomas; Covington, Theresa; Hauck, Fern R.; Kemp, James; MacDorman, Marian

2015-01-01

Sudden unexpected infant deaths (SUID) accounted for 1 in 3 postneonatal deaths in 2010. Sudden infant death syndrome and accidental sleep-related suffocation are among the most frequently reported types of SUID. The causes of these SUID usually are not obvious before a medico-legal investigation and may remain unexplained even after investigation. Lack of consistent investigation practices and an autopsy marker make it difficult to distinguish sudden infant death syndrome from other SUID. Standardized categories might assist in differentiating SUID subtypes and allow for more accurate monitoring of the magnitude of SUID, as well as an enhanced ability to characterize the highest risk groups. To capture information about the extent to which cases are thoroughly investigated and how factors like unsafe sleep may contribute to deaths, CDC created a multistate SUID Case Registry in 2009. As part of the registry, the Centers for Disease Control and Prevention developed a classification system that recognizes the uncertainty about how suffocation or asphyxiation may contribute to death and that accounts for unknown and incomplete information about the death scene and autopsy. This report describes the classification system, including its definitions and decision-making algorithm, and applies the system to 436 US SUID cases that occurred in 2011 and were reported to the registry. These categories, although not replacing official cause-of-death determinations, allow local and state programs to track SUID subtypes, creating a valuable tool to identify gaps in investigation and inform SUID reduction strategies. PMID:24913798

Causes of Mortality among American College Students: A Pilot Study

ERIC Educational Resources Information Center

Turner, James C.; Leno, E. Victor; Keller, Adrienne

2013-01-01

This pilot study from self-selected institutions of higher education provides an estimate of the causes and rates of mortality among college students between the ages of 18 and 24 years old. One hundred fifty-seven 4-year colleges participated in an online survey of student deaths during one academic year. A total of 254 deaths were reported. The…

Caspase inhibitors protect neurons by enabling selective necroptosis of inflamed microglia.

PubMed

Fricker, Michael; Vilalta, Anna; Tolkovsky, Aviva M; Brown, Guy C

2013-03-29

Microglia are resident brain macrophages, which can cause neuronal loss when activated in infectious, ischemic, traumatic, and neurodegenerative diseases. Caspase-8 has both prodeath and prosurvival roles, mediating apoptosis and/or preventing RIPK1-mediated necroptosis depending on cell type and stimulus. We found that inflammatory stimuli (LPS, lipoteichoic acid, or TNF-α) caused an increase in caspase-8 IETDase activity in primary rat microglia without inducing apoptosis. Inhibition of caspase-8 with either Z-VAD-fmk or IETD-fmk resulted in necrosis of activated microglia. Inhibition of caspases with Z-VAD-fmk did not kill non-activated microglia, or astrocytes and neurons in any condition. Necrostatin-1, a specific inhibitor of RIPK1, prevented microglial caspase inhibition-induced death, indicating death was by necroptosis. In mixed cerebellar cultures of primary neurons, astrocytes, and microglia, LPS induced neuronal loss that was prevented by inhibition of caspase-8 (resulting in microglial necroptosis), and neuronal death was restored by rescue of microglia with necrostatin-1. We conclude that the activation of caspase-8 in inflamed microglia prevents their death by necroptosis, and thus, caspase-8 inhibitors may protect neurons in the inflamed brain by selectively killing activated microglia.

Surveillance for leptospirosis in the Americas, 1996–2005: a review of data from ministries of health

PubMed Central

Costa, Federico; Martinez-Silveira, Martha Silvia; Hagan, José E.; Hartskeerl, Rudy A.; dos Reis, Mitermayer Galvão; Ko, Albert Icksang

2014-01-01

Objective To characterize current leptospirosis reporting practices in the Americas. Methods Information was collected from the official websites of national ministries of health from the Americas region and two international organizations; personal communications; and three international morbidity databases. For all sources other than the morbidity databases, the review was limited to official reports citing clinically suspected and laboratory confirmed leptospirosis cases or deaths during the period 1996–2005. Results A total of 73 out of 1 644 reports met the selection criteria and were included in the analysis. Published leptospirosis data were available from half of the countries/sovereign territories (24 out of 48), and 18 of them had mandatory notification policies for leptospirosis. The sum of the median number of leptospirosis cases notified annually by the 24 countries/territories was 4 713.5, but just three countries (Brazil, Costa Rica, and Cuba) accounted for 83.1% (3 920 cases) of the notifications. Eight (16.7%) countries reported deaths due to leptospirosis. The sum of the median number of deaths reported annually for the eight countries was 380, but 349 (91.8%) were reported by Brazil. Conclusions Notification practices in the Americas for leptospirosis are limited. Therefore, the numbers of cases and deaths reported are not representative for the region. The lack of leptospirosis data for many countries/territories may reflect weaknesses in certain aspects of national surveillance systems, including mandatory reporting policies, clinical laboratory infrastructure for performing case confirmation, and capacity to collect reported cases. Improved surveillance of leptospirosis cases and deaths in the Americas is needed to allow monitoring of regional epidemiological patterns and to estimate the burden of this important disease. PMID:23183556

Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line.

PubMed

Thomas, Andrew J; Hailey, Dale W; Stawicki, Tamara M; Wu, Patricia; Coffin, Allison B; Rubel, Edwin W; Raible, David W; Simon, Julian A; Ou, Henry C

2013-03-06

Cisplatin, one of the most commonly used anticancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analog of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line.

Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections.

PubMed

Nichols, Nicole L; Vinit, Stéphane; Bauernschmidt, Lorene; Mitchell, Gordon S

2015-05-01

Amyotrophic lateral sclerosis (ALS) causes progressive motor neuron degeneration, paralysis and death by ventilatory failure. In rodent ALS models: 1) breathing capacity is preserved until late in disease progression despite major respiratory motor neuron death, suggesting unknown forms of compensatory respiratory plasticity; and 2) spinal microglia become activated in association with motor neuron cell death. Here, we report a novel experimental model to study the impact of respiratory motor neuron death on compensatory responses without many complications attendant to spontaneous motor neuron disease. In specific, we used intrapleural injections of cholera toxin B fragment conjugated to saporin (CTB-SAP) to selectively kill motor neurons with access to the pleural space. Motor neuron survival, CD11b labeling (microglia), ventilatory capacity and phrenic motor output were assessed in rats 3-28days after intrapleural injections of: 1) CTB-SAP (25 and 50μg), or 2) unconjugated CTB and SAP (i.e. control; (CTB+SAP). CTB-SAP elicited dose-dependent phrenic and intercostal motor neuron death; 7days post-25μg CTB-SAP, motor neuron survival approximated that in end-stage ALS rats (phrenic: 36±7%; intercostal: 56±10% of controls; n=9; p<0.05). CTB-SAP caused minimal cell death in other brainstem or spinal cord regions. 1) increased CD11b fractional area in the phrenic motor nucleus, indicating microglial activation; 2) decreased breathing during maximal chemoreceptor stimulation; and 3) diminished phrenic motor output in anesthetized rats (7days post-25μg, 0.3±0.07V; CTB+SAP: 1.5±0.3; n=9; p<0.05). Intrapleural CTB-SAP represents a novel, inducible model of respiratory motor neuron death and provides an opportunity to study compensation for respiratory motor neuron loss. Copyright © 2014 Elsevier Inc. All rights reserved.

Electronic Certification of Death in Slovenia - System Considerations and Development Opportunities.

PubMed

Stanimirovic, Dalibor

2016-01-01

Accurate and consistent death certification facilitates morbidity and mortality surveillance, and consequently supports evidence-informed health policies. The paper initially explores the current death certification practice in Slovenia, and identifies related deficiencies and system inconsistencies. Finally, the paper outlines a conceptualization of ICT-based model of death certification including renovation of business processes and organizational changes. The research is based on focus group methodology. Structured discussions were conducted with 29 experts from cross-sectional areas related to death certification. Research results imply that effective ICT-based transformation of the existing death certification model should involve a redefinition of functions and relationships between the main actors, as well as a reconfiguration of the technological, organizational, and regulatory elements in the field. The paper provides an insight into the complexities of the death certification and may provide the groundwork for ICT-based transformation of the death certification model in Slovenia.

A comparison of death recording by health centres and civil registration in South Africans receiving antiretroviral treatment.

PubMed

Johnson, Leigh F; Dorrington, Rob E; Laubscher, Ria; Hoffmann, Christopher J; Wood, Robin; Fox, Matthew P; Cornell, Morna; Schomaker, Michael; Prozesky, Hans; Tanser, Frank; Davies, Mary-Ann; Boulle, Andrew

2015-01-01

There is uncertainty regarding the completeness of death recording by civil registration and by health centres in South Africa. This paper aims to compare death recording by the two systems, in cohorts of South African patients receiving antiretroviral treatment (ART). Completeness of death recording was estimated using a capture-recapture approach. Six ART programmes linked their patient record systems to the vital registration system using civil identity document (ID) numbers and provided data comparing the outcomes recorded in patient files and in the vital registration. Patients were excluded if they had missing/invalid IDs or had transferred to other ART programmes. After exclusions, 91,548 patient records were included. Of deaths recorded in patients files after 2003, 94.0% (95% CI: 93.3-94.6%) were recorded by civil registration, with completeness being significantly higher in urban areas, older adults and females. Of deaths recorded by civil registration after 2003, only 35.0% (95% CI: 34.2-35.8%) were recorded in patient files, with this proportion dropping from 60% in 2004-2005 to 30% in 2010 and subsequent years. Recording of deaths in patient files was significantly higher in children and in locations within 50 km of the health centre. When the information from the two systems was combined, an estimated 96.2% of all deaths were recorded (93.5% in children and 96.2% in adults). South Africa's civil registration system has achieved a high level of completeness in the recording of mortality. However, the fraction of deaths recorded by health centres is low and information from patient records is insufficient by itself to evaluate levels and predictors of ART patient mortality. Previously documented improvements in ART mortality over time may be biased if based only on data from patient records.

Selective inhibition of FLICE-like inhibitory protein expression with small interfering RNA oligonucleotides is sufficient to sensitize tumor cells for TRAIL-induced apoptosis.

PubMed Central

Siegmund, Daniela; Hadwiger, Philipp; Pfizenmaier, Klaus; Vornlocher, Hans-Peter; Wajant, Harald

2002-01-01

BACKGROUND: Most tumors express death receptors and their activation represents a potential selective approach in cancer treatment. The most promising candidate for tumor selective death receptor-activation is tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L, which activates the death receptors TRAIL-R1 and TRAIL-R2, and induces apoptosis preferentially in tumor cells but not in normal tissues. However, many cancer cells are not or only moderately sensitive towards TRAIL and require cotreatment with irradiation or chemotherapy to yield a therapeutically reasonable apoptotic response. Because chemotherapy can have a broad range of unwanted side effects, more specific means for sensitizing tumor cells for TRAIL are desirable. The expression of the cellular FLICE-like inhibitory protein (cFLIP) is regarded as a major cause of TRAIL resistance. We therefore analyzed the usefulness of targeting FLIP to sensitize tumor cells for TRAIL-induced apoptosis. MATERIALS AND METHODS: To selectively interfere with expression of cFLIP short double-stranded RNA oligonucleotides (small interfering RNAs [siRNAs]) were introduced in the human cell lines SV80 and KB by electroporation. Effects of siRNA on FLIP expression were analyzed by Western blotting and RNase protection assay and correlated with TRAIL sensitivity upon stimulation with recombinant soluble TRAIL and TRAIL-R1- and TRAIL-R2-specific agonistic antibodies. RESULTS: FLIP expression can be inhibited by RNA interference using siRNAs, evident from reduced levels of FLIP-mRNA and FLIP protein. Inhibition of cFLIP expression sensitizes cells for apoptosis induction by TRAIL and other death ligands. In accordance with the presumed function of FLIP as an inhibitor of death receptor-induced caspase-8 activation, down-regulation of FLIP by siRNAs enhanced TRAIL-induced caspase-8 activation. CONCLUSION: Inhibition of FLIP expression was sufficient to sensitize tumor cells for TRAIL-induced apoptosis. The combination of TRAIL and FLIP-targeting siRNA could therefore be a useful strategy to attack cancer cells, which are resistant to TRAIL alone. PMID:12520089

Attitudes toward clinical autopsy in unexpected patient deaths in Japan: a nation-wide survey of the general public and physicians.

PubMed

Kamishiraki, Etsuko; Maeda, Shoichi; Starkey, Jay; Ikeda, Noriaki

2012-12-01

Autopsy is a useful tool for understanding the cause and manner of unexpected patient death. However, the attitudes of the general public and physicians in Japan about clinical autopsy are limited. To describe the beliefs of the general public about whether autopsy should be performed and ascertain if they would actually request one given specific clinical situations where patient death occurred with the additional variable of medical error. To compare these attitudes with previously obtained attitudes of physicians practising at Japanese teaching hospitals. We conducted a cross-sectional study of the general public. We sent standardised questionnaires in 2010 to a randomly selected non-physician adult population using a survey company for participant selection. Respondents gave their opinions about the necessity of autopsy and how they might act given various clinical scenarios of patient death. We compared these results with those of a previous survey of Japanese physicians conducted in 2009. Of the 2300 eligible general adult population, 1575 (68.5%) responded. The majority of the general public indicated they believed an autopsy was necessary. However, in cases of unclear medical error or unclear cause and effect relationship of medical care and patient death, the general public were much less likely to indicate they would actually request an autopsy than were physicians (p<0.0001). Currently in Japan the debate about the role autopsy should play in the case of error related to death is underway. The results from this study will be important in informing related decisions.

Human-gyrovirus-Apoptin triggers mitochondrial death pathway--Nur77 is required for apoptosis triggering.

PubMed

Chaabane, Wiem; Cieślar-Pobuda, Artur; El-Gazzah, Mohamed; Jain, Mayur V; Rzeszowska-Wolny, Joanna; Rafat, Mehrdad; Stetefeld, Joerg; Ghavami, Saeid; Los, Marek J

2014-09-01

The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, triggers apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD (fas-associated death domain) function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of apoptotic protease-activating factor 1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin-induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin-induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin-induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together these data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction

NASA Astrophysics Data System (ADS)

Nadine Wong Shi Kam,; O'Connell, Michael; Wisdom, Jeffrey A.; Dai, Hongjie

2005-08-01

Biological systems are known to be highly transparent to 700- to 1,100-nm near-infrared (NIR) light. It is shown here that the strong optical absorbance of single-walled carbon nanotubes (SWNTs) in this special spectral window, an intrinsic property of SWNTs, can be used for optical stimulation of nanotubes inside living cells to afford multifunctional nanotube biological transporters. For oligonucleotides transported inside living cells by nanotubes, the oligos can translocate into cell nucleus upon endosomal rupture triggered by NIR laser pulses. Continuous NIR radiation can cause cell death because of excessive local heating of SWNT in vitro. Selective cancer cell destruction can be achieved by functionalization of SWNT with a folate moiety, selective internalization of SWNTs inside cells labeled with folate receptor tumor markers, and NIR-triggered cell death, without harming receptor-free normal cells. Thus, the transporting capabilities of carbon nanotubes combined with suitable functionalization chemistry and their intrinsic optical properties can lead to new classes of novel nanomaterials for drug delivery and cancer therapy. Author contributions: N.W.S.K., M.O., and H.D. designed research; N.W.S.K., M.O., and J.A.W. performed research; N.W.S.K., M.O., and H.D. analyzed data; and N.W.S.K. and H.D. wrote the paper.This paper was submitted directly (Track II) to the PNAS office.Abbreviations: NIR, near-infrared; SWNT, single-walled carbon nanotube; AFM, atomic force microscopy; PL, phospholipid; PEG, polyethylene glycol; FA, folic acid; FR, folate receptor.

Selective Androgen Receptor Modulator RAD140 Is Neuroprotective in Cultured Neurons and Kainate-Lesioned Male Rats

PubMed Central

Jayaraman, Anusha; Christensen, Amy; Moser, V. Alexandra; Vest, Rebekah S.; Miller, Chris P.; Hattersley, Gary

2014-01-01

The decline in testosterone levels in men during normal aging increases risks of dysfunction and disease in androgen-responsive tissues, including brain. The use of testosterone therapy has the potential to increase the risks for developing prostate cancer and or accelerating its progression. To overcome this limitation, novel compounds termed “selective androgen receptor modulators” (SARMs) have been developed that lack significant androgen action in prostate but exert agonist effects in select androgen-responsive tissues. The efficacy of SARMs in brain is largely unknown. In this study, we investigate the SARM RAD140 in cultured rat neurons and male rat brain for its ability to provide neuroprotection, an important neural action of endogenous androgens that is relevant to neural health and resilience to neurodegenerative diseases. In cultured hippocampal neurons, RAD140 was as effective as testosterone in reducing cell death induced by apoptotic insults. Mechanistically, RAD140 neuroprotection was dependent upon MAPK signaling, as evidenced by elevation of ERK phosphorylation and inhibition of protection by the MAPK kinase inhibitor U0126. Importantly, RAD140 was also neuroprotective in vivo using the rat kainate lesion model. In experiments with gonadectomized, adult male rats, RAD140 was shown to exhibit peripheral tissue-specific androgen action that largely spared prostate, neural efficacy as demonstrated by activation of androgenic gene regulation effects, and neuroprotection of hippocampal neurons against cell death caused by systemic administration of the excitotoxin kainate. These novel findings demonstrate initial preclinical efficacy of a SARM in neuroprotective actions relevant to Alzheimer's disease and related neurodegenerative diseases. PMID:24428527

Epidemiological Characteristics and Underlying Risk Factors for Mortality during the Autumn 2009 Pandemic Wave in Mexico

PubMed Central

Chowell, Gerardo; Echevarría-Zuno, Santiago; Viboud, Cécile; Simonsen, Lone; Miller, Mark A.; Fernández-Gárate, Irma; González-Bonilla, Cesar; Borja-Aburto, Víctor H.

2012-01-01

Background Elucidating the role of the underlying risk factors for severe outcomes of the 2009 A/H1N1 influenza pandemic could be crucial to define priority risk groups in resource-limited settings in future pandemics. Methods We use individual-level clinical data on a large series of ARI (acute respiratory infection) hospitalizations from a prospective surveillance system of the Mexican Social Security medical system to analyze clinical features at presentation, admission delays, selected comorbidities and receipt of seasonal vaccine on the risk of A/H1N1-related death. We considered ARI hospitalizations and inpatient-deaths, and recorded demographic, geographic, and medical information on individual patients during August-December, 2009. Results Seasonal influenza vaccination was associated with a reduced risk of death among A/H1N1 inpatients (OR = 0.43 (95% CI: 0.25, 0.74)) after adjustment for age, gender, geography, antiviral treatment, admission delays, comorbidities and medical conditions. However, this result should be interpreted with caution as it could have been affected by factors not directly measured in our study. Moreover, the effect of antiviral treatment against A/H1N1 inpatient death did not reach statistical significance (OR = 0.56 (95% CI: 0.29, 1.10)) probably because only 8.9% of A/H1N1 inpatients received antiviral treatment. Moreover, diabetes (OR = 1.6) and immune suppression (OR = 2.3) were statistically significant risk factors for death whereas asthmatic persons (OR = 0.3) or pregnant women (OR = 0.4) experienced a reduced fatality rate among A/H1N1 inpatients. We also observed an increased risk of death among A/H1N1 inpatients with admission delays >2 days after symptom onset (OR = 2.7). Similar associations were also observed for A/H1N1-negative inpatients. Conclusions Geographical variation in identified medical risk factors including prevalence of diabetes and immune suppression may in part explain between-country differences in pandemic mortality burden. Furthermore, access to care including hospitalization without delay and antiviral treatment and are also important factors, as well as vaccination coverage with the 2008–09 trivalent inactivated influenza vaccine. PMID:22815917

Lost life years due to premature mortality caused by diseases of the respiratory system.

PubMed

Maniecka-Bryła, Irena; Paciej-Gołębiowska, Paulina; Dziankowska-Zaborszczyk, Elżbieta; Bryła, Marek

2018-06-04

In Poland, as in most other European countries, diseases of the respiratory system are the 4th leading cause of mortality; they are responsible for about 8% of all deaths in the European Union (EU) annually. To assess the socio-economic aspects of mortality, it has become increasingly common to apply potential measures rather than conventionally used ratios. The aim of this study was to analyze years of life lost due to premature deaths caused by diseases of the respiratory system in Poland from 1999 to 2013. The study was based on a dataset of 5,606,516 records, obtained from the death certificates of Polish residents who died between 1999 and 2013. The information on deaths caused by diseases of the respiratory system, i.e., coded as J00-J99 according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10), was analyzed. The Standard Expected Years of Life Lost (SEYLL) indicator was used in the study. In the years 1999-2013, the Polish population suffered 280,519 deaths caused by diseases of the respiratory system (4.69% of all deaths). In the period analyzed, a gradual decrease in the standardized death rate was observed - from 46.31 per 100,000 inhabitants in 1999 to 41.02 in 2013. The dominant causes of death were influenza and pneumonia (J09-J18) and chronic lower respiratory diseases (J40-J47). Diseases of the respiratory system were the cause of 4,474,548.92 lost life years. The Standard Expected Years of Life Lost per person (SEYLLp) was 104.72 per 10,000 males and 52.85 per 10,000 females. The Standard Expected Years of Life Lost per death (SEYLLd) for people who died due to diseases of the respiratory system was 17.54 years of life on average for men and 13.65 years on average for women. The use of the SEYLL indicator provided significant information on premature mortality due to diseases of the respiratory system, indicating the fact that they play a large role in the health status of the Polish population.

Epitome of China's unnatural deaths: a historically retrospective study of forensic autopsy cases in Shanghai Public Security Bureau from 1990 to 1999.

PubMed

He, Meng; Li, Wen-Can; Sun, Da-Ming; Ma, Kai-Jun; Zhao, Zi-Qin; Li, Bei-Xu; Li, Ling

2014-09-01

The unnatural death investigation in China seems vague to the world. Shanghai is one of the largest city located in Yangtze River Delta in the East China. This study is committed to lift the veil of unnatural death investigation and describe the epitome of China's unnatural deaths. Based on the 7302 forensic report archives from 1990 to 1999 in Shanghai Public Security Bureau, statistics were carried out in 5 areas according to the manner of death. In 3502 accidental deaths, there was a rapid increase during the 1990s, and 71.6% were involved in traffic accidents whose major cause of death was head and neck injuries. The first 3 causes of death in nontraffic accidents (994) were head and neck injuries (42.8%), poisoning (11.8%), and drowning (9.0%). In 2456 homicides, sharp force injury (36.7%), blunt force injury (35.8%), and manual strangulation (12.9%) were the first 3 causes of death. In 563 suicides, drug/chemical intoxication (40.1%), hanging (23.4%), and injuries because of fall from height (11.4%) were the 3 leading causes of death, especially pesticides ingestion. The causes of natural deaths were diseases mainly in circulatory system (23.1%), central nervous system (12.8%), and respiratory system (6.4%). However, the cause of death remained undetermined in 500 victims. Childhood fatalities were different. The victims of accidents and homicides were nearly equal, and the main cause of homicide was manual strangulation. Besides, 1997 was the landmark year when drug abuse began to emerge in Shanghai.

Burden of Violent Death on Years of Life Lost in Rhode Island, 2006-2013.

PubMed

Jiang, Yongwen; Ranney, Megan L; Perez, Beatriz; Viner-Brown, Samara

2016-11-01

Mortality from injuries, particularly violent injuries, is more common among the young. Although traditional epidemiologic measures describe burden of death using rate-related mortalities, this method may not accurately represent burden of premature death. Years of life lost (YLLs) incorporate time discounting and age weighting to more accurately estimate the burden of death. To the authors' knowledge, there has been no examination of YLLs using the Rhode Island Violent Death Reporting System data. This study's objective was to assess the burden of violent death in Rhode Island in terms of YLLs. This study used 2006-2013 Rhode Island Violent Death Reporting System data. YLLs as a result of premature violent deaths were assessed overall and by age, sex, race/ethnicity, and manner of death. Data were analyzed in 2015. Suicide made the largest contribution to the overall YLLs (61.3%), followed by homicide (24.0%), whereas undetermined intent deaths captured by the system accounted for 14.8% of YLLs. In Rhode Island, people aged 25-44 years had the highest YLLs due to suicide, and Hispanics had the highest YLLs due to homicide/legal intervention. By comparison, using crude mortality rate calculations, people aged 45-64 years had the highest suicide mortality rate and non-Hispanic blacks had the highest homicide mortality rate. YLL calculations provide a different picture than crude mortality-based assessments of the population at highest risk for violent death. This study demonstrates the strengths of using YLL to assess the burden of violent death at the state level. Published by Elsevier Inc.

Non-locality Sudden Death in Tripartite Systems

NASA Astrophysics Data System (ADS)

Jaeger, Gregg; Ann, Kevin

2009-03-01

Bell non-locality sudden death is the disappearance of non-local properties in finite times under local phase noise, which decoheres states only in the infinite-time limit. We consider the relationship between decoherence, disentanglement, and Bell non-locality sudden death in bipartite and tripartite systems in specific large classes of state preparation.

Child Maltreatment Fatalities in Children under 5: Findings from the National Violence Death Reporting System

ERIC Educational Resources Information Center

Klevens, Joanne; Leeb, Rebecca T.

2010-01-01

Objective: To describe the distribution of child maltreatment fatalities of children under 5 by age, sex, race/ethnicity, type of maltreatment, and relationship to alleged perpetrator using data from the National Violent Death Reporting System (NVDRS). Study design: Two independent coders reviewed information from death certificates, medical…

Mortality from systemic erythematosus lupus in Brazil: evaluation of causes according to the government health database.

PubMed

Costi, Luisa Ribeiro; Iwamoto, Hatsumi Miyashiro; Neves, Dilma Costa de Oliveira; Caldas, Cezar Augusto Muniz

To characterize the causes of mortality in patients with systemic lupus erythematosus (SLE) in Brazil between 2002 and 2011. An exploratory ecological study of a time series using data from the Mortality Information System of DATASUS, the Department of the Unified Health System (Brazil's National Health System). Brazil's SLE mortality rate was 4.76 deaths/10 5 inhabitants. The mortality rate was higher in the Midwest, North and Southeast regions than in the country as a whole. There were 6.3% fewer and 4.2% more deaths than expected in the Northeast and Southeast regions, respectively. The mean age at death was 40.7±18 years, and 45.61% of deaths occurred between the ages of 20 and 39. Incidence was highest in women (90.7%) and whites (49.2%). Disorders of the musculoskeletal system and connective tissue were mentioned as an underlying cause of death in 77.5% of cases, and diseases of the circulatory system and infectious and parasitic diseases were also noted in fewer cases. SLE was mentioned as an underlying cause of death in 77% of cases, with no difference between the Brazilian regions (p=0.2058). The main SLE-related causes of death were, sequentially, diseases of the respiratory and circulatory systems and infectious and parasitic diseases. This study identified a need for greater control of risk factors for cardiovascular diseases and a better understanding of the pathogenesis of atherosclerosis in SLE. Infectious causes are still frequent, and management should be improved, especially in the early stages of the disease. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

[Impact of heat waves on non-accidental deaths in Jinan, China].

PubMed

Zhang, J; Liu, S Q; Zhou, L; Gong, S P; Liu, Y L; Zhang, Y; Zhang, J

2016-02-20

To assess the impact of heat waves on non-accidental deaths, and to investigate the influencing factors for deaths caused by heat waves in Jinan, China. Daily death data and meteorological data for summer days with or without heat waves in Jinan from 2012 to 2014 were collected, and a cross-over analysis was conducted to evaluate the influence of heat waves on non-accidental deaths and deaths caused by other reasons. The univariate and multivariate logistic regression models were used to investigate the influencing factors for deaths caused by heat waves. The risks of non-accidental deaths and deaths caused by circulation system diseases during the days with heat waves were 1.82 times(95% CI: 1.47~2.36) and 1.53 times(95% CI: 1.14~2.07) those during the days without heat waves. The multivariate logistic regression analysis showed that old age(≥75 years)(OR=1.184, 95% CI: 1.068~1.313), low educational level(OR=1.187, 95% CI: 1.064~1.324), and deaths outside hospital(OR=1.105, 95% CI: 1.009~1.210) were associated with the high risk of deaths during the days with heat waves. Heat waves significantly increase the risk of non-accidental deaths and deaths caused by circulation system diseases in Jinan, and the deaths during the days with heat waves are related to age, educational level, and place of death.

[Assessment of three-level selective perinatal care based on the analysis of early perinatal death rates and cesarean sections in Poland in 2008].

PubMed

Troszyński, Michał; Niemiec, Tomasz; Wilczyńska, Anna

2009-09-01

The aim of the following work was to assess three-level selective perinatal care in Polish voivodeships in 2008 on the basis of the following parameters: birth rates as well as perinatal death rates, divided into three classes of neonatal weights, in hospitals on each of the three levels. The goal of selective perinatal care is, among other things, to diagnose threats to the mother and/or fetus and direct women with high-risk pregnancies to higher level obstetrics and neonatology clinics and units. The structure of a regional three-level perinatal care, as well as the rules and procedures governing the process of redirecting patients to different levels of perinatal care have been defined in great detail. Perinatal death rates analysis has been carried out on the basis of data received from Voivodeship Public Health Centers in sixteen voivodeships in Poland in 2008. The main document constituted MZ-29 form section X, modified by the authors and subdivided into levels of perinatal care. All data contained in the form have been verified: the numbers concerning birth and death rates as well as perinatal deaths and birth weight subgroups from given voivodeship hospitals. Statistic analysis was limited to the presentation of result tables and graphs within voivodeships. Birth rates and perinatal death rates revealed that in the course of ten years the level of perinatal care, introduced gradually in Poland between the years 1997-1999, resulted in its improvement. Perinatal death rates decreased in the course of ten years from 9.5% in 1999 to 6.45% in 2008, i.e. by 0.3% annually. On the first level, the rate of neonates with very low birth weight, 500-999g, decreased by 5.5% and was 21.1% in 2008 and 36.6% in 1999, whereas on the third level, the birth rate in the same group (500-999g) increased by 12.7% and was 47.7% in 2008 and 35.5% in 1999. There is a growing and alarming tendency to perform cesarean sections. The increase amounted up to 1.2% annually (18.2% in 19999 and 30.5% in 2008), with vast differences among hospitals and voivodeships. In 2008 there were 28.4% of cesarean sections in level one-hospitals, 29.3% in level two-hospitals and 40.6% in level three-hospitals. The results of an overall decrease in perinatal deaths rate and an increase in birth rates in the group of neonates with very low birth weight on the third level are not satisfactory. Reintroduction of the program and strategy from the years 1995 and 1997 will enable us to improve the situation. Particularly this should be the case on the basic level perinatal care. In the context of three-level selective strategy the reintroduction of periodical analysis of perinatal care results is essential.

Electronic palliative care coordination systems: Devising and testing a methodology for evaluating documentation

PubMed Central

Allsop, Matthew J; Kite, Suzanne; McDermott, Sarah; Penn, Naomi; Millares-Martin, Pablo; Bennett, Michael I

2016-01-01

Background: The need to improve coordination of care at end of life has driven electronic palliative care coordination systems implementation across the United Kingdom and internationally. No approaches for evaluating electronic palliative care coordination systems use in practice have been developed. Aim: This study outlines and applies an evaluation framework for examining how and when electronic documentation of advance care planning is occurring in end of life care services. Design: A pragmatic, formative process evaluation approach was adopted. The evaluation drew on the Project Review and Objective Evaluation methodology to guide the evaluation framework design, focusing on clinical processes. Setting/participants: Data were extracted from electronic palliative care coordination systems for 82 of 108 general practices across a large UK city. All deaths (n = 1229) recorded on electronic palliative care coordination systems between April 2014 and March 2015 were included to determine the proportion of all deaths recorded, median number of days prior to death that key information was recorded and observations about routine data use. Results: The evaluation identified 26.8% of all deaths recorded on electronic palliative care coordination systems. The median number of days to death was calculated for initiation of an electronic palliative care coordination systems record (31 days), recording a patient’s preferred place of death (8 days) and entry of Do Not Attempt Cardiopulmonary Resuscitation decisions (34 days). Where preferred and actual place of death was documented, these were matching for 75% of patients. Anomalies were identified in coding used during data entry on electronic palliative care coordination systems. Conclusion: This study reports the first methodology for evaluating how and when electronic palliative care coordination systems documentation is occurring. It raises questions about what can be drawn from routine data collected through electronic palliative care coordination systems and outlines considerations for future evaluation. Future evaluations should consider work processes of health professionals using electronic palliative care coordination systems. PMID:27507636

Electronic palliative care coordination systems: Devising and testing a methodology for evaluating documentation.

PubMed

Allsop, Matthew J; Kite, Suzanne; McDermott, Sarah; Penn, Naomi; Millares-Martin, Pablo; Bennett, Michael I

2017-05-01

The need to improve coordination of care at end of life has driven electronic palliative care coordination systems implementation across the United Kingdom and internationally. No approaches for evaluating electronic palliative care coordination systems use in practice have been developed. This study outlines and applies an evaluation framework for examining how and when electronic documentation of advance care planning is occurring in end of life care services. A pragmatic, formative process evaluation approach was adopted. The evaluation drew on the Project Review and Objective Evaluation methodology to guide the evaluation framework design, focusing on clinical processes. Data were extracted from electronic palliative care coordination systems for 82 of 108 general practices across a large UK city. All deaths ( n = 1229) recorded on electronic palliative care coordination systems between April 2014 and March 2015 were included to determine the proportion of all deaths recorded, median number of days prior to death that key information was recorded and observations about routine data use. The evaluation identified 26.8% of all deaths recorded on electronic palliative care coordination systems. The median number of days to death was calculated for initiation of an electronic palliative care coordination systems record (31 days), recording a patient's preferred place of death (8 days) and entry of Do Not Attempt Cardiopulmonary Resuscitation decisions (34 days). Where preferred and actual place of death was documented, these were matching for 75% of patients. Anomalies were identified in coding used during data entry on electronic palliative care coordination systems. This study reports the first methodology for evaluating how and when electronic palliative care coordination systems documentation is occurring. It raises questions about what can be drawn from routine data collected through electronic palliative care coordination systems and outlines considerations for future evaluation. Future evaluations should consider work processes of health professionals using electronic palliative care coordination systems.

Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans

PubMed Central

Coburn, Cassandra; Allman, Erik; Mahanti, Parag; Benedetto, Alexandre; Cabreiro, Filipe; Pincus, Zachary; Matthijssens, Filip; Araiz, Caroline; Mandel, Abraham; Vlachos, Manolis; Edwards, Sally-Anne; Fischer, Grahame; Davidson, Alexander; Pryor, Rosina E.; Stevens, Ailsa; Slack, Frank J.; Tavernarakis, Nektarios; Braeckman, Bart P.; Schroeder, Frank C.; Nehrke, Keith; Gems, David

2013-01-01

For cells the passage from life to death can involve a regulated, programmed transition. In contrast to cell death, the mechanisms of systemic collapse underlying organismal death remain poorly understood. Here we present evidence of a cascade of cell death involving the calpain-cathepsin necrosis pathway that can drive organismal death in Caenorhabditis elegans. We report that organismal death is accompanied by a burst of intense blue fluorescence, generated within intestinal cells by the necrotic cell death pathway. Such death fluorescence marks an anterior to posterior wave of intestinal cell death that is accompanied by cytosolic acidosis. This wave is propagated via the innexin INX-16, likely by calcium influx. Notably, inhibition of systemic necrosis can delay stress-induced death. We also identify the source of the blue fluorescence, initially present in intestinal lysosome-related organelles (gut granules), as anthranilic acid glucosyl esters—not, as previously surmised, the damage product lipofuscin. Anthranilic acid is derived from tryptophan by action of the kynurenine pathway. These findings reveal a central mechanism of organismal death in C. elegans that is related to necrotic propagation in mammals—e.g., in excitotoxicity and ischemia-induced neurodegeneration. Endogenous anthranilate fluorescence renders visible the spatio-temporal dynamics of C. elegans organismal death. PMID:23935448

Costs Associated with Implementation of Computer-Assisted Clinical Decision Support System for Antenatal and Delivery Care: Case Study of Kassena-Nankana District of Northern Ghana

PubMed Central

Dalaba, Maxwell Ayindenaba; Akweongo, Patricia; Williams, John; Saronga, Happiness Pius; Tonchev, Pencho; Sauerborn, Rainer; Mensah, Nathan; Blank, Antje; Kaltschmidt, Jens; Loukanova, Svetla

2014-01-01

Objective This study analyzed cost of implementing computer-assisted Clinical Decision Support System (CDSS) in selected health care centres in Ghana. Methods A descriptive cross sectional study was conducted in the Kassena-Nankana district (KND). CDSS was deployed in selected health centres in KND as an intervention to manage patients attending antenatal clinics and the labour ward. The CDSS users were mainly nurses who were trained. Activities and associated costs involved in the implementation of CDSS (pre-intervention and intervention) were collected for the period between 2009–2013 from the provider perspective. The ingredients approach was used for the cost analysis. Costs were grouped into personnel, trainings, overheads (recurrent costs) and equipment costs (capital cost). We calculated cost without annualizing capital cost to represent financial cost and cost with annualizing capital costs to represent economic cost. Results Twenty-two trained CDSS users (at least 2 users per health centre) participated in the study. Between April 2012 and March 2013, users managed 5,595 antenatal clients and 872 labour clients using the CDSS. We observed a decrease in the proportion of complications during delivery (pre-intervention 10.74% versus post-intervention 9.64%) and a reduction in the number of maternal deaths (pre-intervention 4 deaths versus post-intervention 1 death). The overall financial cost of CDSS implementation was US$23,316, approximately US$1,060 per CDSS user trained. Of the total cost of implementation, 48% (US$11,272) was pre-intervention cost and intervention cost was 52% (US$12,044). Equipment costs accounted for the largest proportion of financial cost: 34% (US$7,917). When economic cost was considered, total cost of implementation was US$17,128–lower than the financial cost by 26.5%. Conclusions The study provides useful information in the implementation of CDSS at health facilities to enhance health workers' adherence to practice guidelines and taking accurate decisions to improve maternal health care. PMID:25180831

Survey of New York City Resident Physicians on Cause-of-Death Reporting, 2010

PubMed Central

Wexelman, Barbara A.; Eden, Edward

2013-01-01

Introduction Death certificates contain critical information for epidemiology, public health research, disease surveillance, and community health programs. In most teaching hospitals, resident physicians complete death certificates. The objective of this study was to examine the experiences and opinions of physician residents in New York City on the accuracy of the cause-of-death reporting system. Methods In May and June 2010, we conducted an anonymous, Internet-based, 32-question survey of all internal medicine, emergency medicine, and general surgery residency programs (n = 70) in New York City. We analyzed data by type of residency and by resident experience in reporting deaths. We defined high-volume respondents as those who completed 11 or more death certificates in the last 3 years. Results A total of 521 residents from 38 residency programs participated (program response rate, 54%). We identified 178 (34%) high-volume respondents. Only 33.3% of all respondents and 22.7% of high-volume residents believed that cause-of-death reporting is accurate. Of all respondents, 48.6% had knowingly reported an inaccurate cause of death; 58.4% of high-volume residents had done so. Of respondents who indicated they reported an inaccurate cause, 76.8% said the system would not accept the correct cause, 40.5% said admitting office personnel instructed them to “put something else,” and 30.7% said the medical examiner instructed them to do so; 64.6% cited cardiovascular disease as the most frequent diagnosis inaccurately reported. Conclusion Most resident physicians believed the current cause-of-death reporting system is inaccurate, often knowingly documenting incorrect causes. The system should be improved to allow reporting of more causes, and residents should receive better training on completing death certificates. PMID:23660118

Different perspectives: a comparison of newspaper articles to medical examiner data in the reporting of violent deaths.

PubMed

Genovesi, Andrea L; Donaldson, Amy E; Morrison, Brynna L; Olson, Lenora M

2010-03-01

This study compared violent death information reported in state-wide newspaper articles to the medical examiner reports collected for a state public health surveillance system-the National Violent Death Reporting System (NVDRS). While suicides accounted for 83% of deaths in the NVDRS database, more than three-quarters (79%) of violent deaths reported in newspaper articles were homicides. The majority of the suicide incidents were reported in 1-2 newspaper articles whereas the majority of homicide incidents were reported in 11-34 articles. For suicide incidents, the NVDRS reported more circumstances related to mental health problems while newspaper articles reported recent crisis more often. Results show that there is a mismatch in both frequency and type of information reported between a public health surveillance system (NVDRS) and newspaper reporting of violent deaths. As a result of these findings, scientists and other public health professionals may want to engage in media advocacy to provide newspaper reporters with timely and important health information related to the prevention and intervention of violent deaths in their community. Copyright 2009 Elsevier Ltd. All rights reserved.

Surveillance for violent deaths--National Violent Death Reporting System, 16 states, 2005.

PubMed

Karch, Debra L; Lubell, Keri M; Friday, Jennifer; Patel, Nimesh; Williams, Dionne D

2008-04-11

An estimated 50,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2005. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2005. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, and law enforcement reports. NVDRS began operation in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004 and four (California, Kentucky, New Mexico, and Utah) in 2005, for a total of 17 states. This report includes data from 16 states; data from California are not included in this report because NVDRS has been implemented only in a limited number of California cities and counties rather than statewide as in other states. For 2005, a total of 15,495 fatal incidents involving 15,962 violent deaths occurred in the 16 NVDRS states included in this report. The majority (56.1%) of deaths were suicides, followed by homicides and deaths involving legal interventions (29.6%), violent deaths of undetermined intent (13.3%), and unintentional firearm deaths (0.7%). Fatal injury rates varied by sex, race/ethnicity, age group, and method of injury. Rates were substantially higher for males than for females and for American Indians/Alaska Natives (AI/ANs) and blacks than for whites and Hispanics. Rates were highest for persons aged 20-24 years. For method of injury, the three highest rates were reported for firearms, poisonings, and hanging/strangulation/suffocation. Suicides occurred at higher rates among males, AI/ANs, whites, and older persons and most often involved the use of firearms in the home. Suicides were precipitated primarily by mental illness, intimate partner or physical health problems, or a crisis during the previous 2 weeks. Homicides occurred at higher rates among males and young adult blacks and most often involved the use of firearms in the home or on a street/highway. Homicides were precipitated primarily by an argument over something other than money or property or in conjunction with another crime. Similar variation was reported among the other manners of death and special situations or populations highlighted in this report. This report provides the first detailed summary of data concerning violent deaths collected by NVDRS. The results indicate that deaths resulting from self-inflicted or interpersonal violence occur to a varying extent among males and females of every age group and racial/ethnic population. Key factors affecting rates of violent fatal injuries include sex, age group, method of injury, location of injury, and precipitating circumstances (e.g., mental health and substance abuse). Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. Accurate, timely, and comprehensive surveillance data are necessary for the occurrence of violent deaths in the United States to be understood better and ultimately prevented. NVDRS data can be used to track the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths and injuries at the national, state, and local levels. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal costs of violence. Further efforts are needed to increase the number of states using NVDRS, with an ultimate goal of full national representation.

Surveillance for violent deaths--National Violent Death Reporting System, 16 states, 2008.

PubMed

Karch, Debra L; Logan, Joseph; Patel, Nimesh

2011-08-26

An estimated 50,000 persons die annually in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 16 U.S. states for 2008. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2008. NVDRS collects data regarding violent deaths obtained from death certificates, coroner/medical examiner reports, and law enforcement reports. NVDRS data collection began in 2003 with seven states (Alaska, Maryland, Massachusetts, New Jersey, Oregon, South Carolina, and Virginia) participating; six states (Colorado, Georgia, North Carolina, Oklahoma, Rhode Island, and Wisconsin) joined in 2004, four (California, Kentucky, New Mexico, and Utah) in 2005, and two in 2010 (Ohio and Michigan) for a total of 19 states. This report includes data from 16 states that collected statewide data in 2008; data from California are not included in this report because NVDRS was implemented only in a limited number of California cities and counties rather than statewide. Ohio and Michigan are excluded because they did not begin data collection until 2010. For 2008, a total of 15,755 fatal incidents involving 16,138 deaths were captured by NVDRS in the 16 states included in this report. The majority (58.7%) of deaths were suicides, followed by homicides and deaths involving legal intervention (i.e. deaths caused by police and other persons with legal authority to use deadly force, excluding legal executions) (26.4%), deaths of undetermined intent (14.5%), and unintentional firearm deaths (0.4%). Suicides occurred at higher rates among males, American Indians/Alaska Natives (AI/ANs), non-Hispanic whites, and persons aged 45-54 years. Suicides occurred most often in a house or apartment (70.6%) and involved the use of firearms (51.5%). Suicides were precipitated primarily by mental health (45.4%), intimate partner (30.9%), or physical health problems (22.6%), or by a crisis during the preceding 2 weeks (27.9%). Homicides occurred at higher rates among males and persons aged 20-24 years; rates were highest among non-Hispanic black males. The majority of homicides involved the use of a firearm (65.8%) and occurred in a house or apartment (52.5%) or on a street/highway (21.3%). Homicides were precipitated primarily by arguments (41.4%) and interpersonal conflicts (18.4%) or in conjunction with another crime (30.2%). Other manners of death and special situations or populations also are highlighted in this report. This report provides a detailed summary of data from NVDRS for 2008. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected adults aged <55 years, males, and certain minority populations. For homicides and suicides, relationship problems, interpersonal conflicts, mental health problems, and recent crises were among the primary precipitating factors. Because additional information might be reported subsequently as participating states update their findings, the data provided in this report are preliminary. For the occurrence of violent deaths in the United States to be better understood and ultimately prevented, accurate, timely, and comprehensive surveillance data are necessary. NVDRS data can be used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths at the national, state, and local levels. The continued development and expansion of NVDRS is essential to CDC's efforts to reduce the personal, familial, and societal costs of violence. Further efforts are needed to increase the number of states participating in NVDRS, with an ultimate goal of full national representation.

The multiple decrement life table: a unifying framework for cause-of-death analysis in ecology.

PubMed

Carey, James R

1989-01-01

The multiple decrement life table is used widely in the human actuarial literature and provides statistical expressions for mortality in three different forms: i) the life table from all causes-of-death combined; ii) the life table disaggregated into selected cause-of-death categories; and iii) the life table with particular causes and combinations of causes eliminated. The purpose of this paper is to introduce the multiple decrement life table to the ecological literature by applying the methods to published death-by-cause information on Rhagoletis pomonella. Interrelations between the current approach and conventional tools used in basic and applied ecology are discussed including the conventional life table, Key Factor Analysis and Abbott's Correction used in toxicological bioassay.

Triazolam blood concentrations in forensic cases in Canada.

PubMed

Joynt, B P

1993-01-01

Triazolam has been a controversial drug since its appearance on world markets as a hypnotic more than ten years ago. Whole blood concentrations of triazolam as found in forensic cases are cited in several categories; that is, impaired driving: 17 cases; sexual assault: four cases; death due to drugs: 45 cases; drug-related death (drugs contributed to the death but were not the ultimate cause): 20 cases; drug-involved death (drugs were present but were not felt to be a contributing factor): six cases; miscellaneous: one case. The data was gleaned from a forensic toxicology database designed and used by the Forensic Toxicology Sections of the Royal Canadian Mounted Police (RCMP) laboratories in Canada. Triazolam concentrations from selected references are included for comparison.

Initial Clinical Experience Using the Low-Profile Altura Endograft System With Double D-Shaped Proximal Stents for Endovascular Aneurysm Repair.

PubMed

Krievins, Dainis; Krämer, Albrecht; Savlovskis, Janis; Oszkinis, Georgij; Debus, E Sebastian; Oberhuber, Alexander; Zarins, Christopher K

2018-06-01

To report the initial clinical results of endovascular aneurysm repair (EVAR) using the low-profile (14-F) Altura Endograft System, which features a double "D-shaped" stent design with suprarenal fixation and modular iliac components that are deployed from distal to proximal. From 2011 to 2015, 90 patients (mean age 72.8±8.3 years; 79 men) with abdominal aortic aneurysm (AAA; mean diameter 53.8±5.7 mm) were treated at 10 clinical sites in 2 prospective, controlled clinical studies using the Altura endograft. Outcomes evaluated included mortality, major adverse events (MAEs: all-cause death, stroke, paraplegia, myocardial infarction, respiratory failure, bowel ischemia, and blood loss ≥1000 mL), and clinical success (freedom from procedure-related death, type I/III endoleak, migration, thrombosis, and reintervention). Endografts were successfully implanted in 89 (99%) patients; the single failure was due to delivery system malfunction before insertion in the early-generation device. One (1%) patient died and 4 patients underwent reinterventions (1 type I endoleak, 2 iliac limb stenoses, and 1 endograft occlusion) within the first 30 days. During a median follow-up of 12.5 months (range 11.5-50.9), there were no aneurysm ruptures, surgical conversions, or AAA-related deaths. The cumulative MAE rates were 3% (3/89) at 6 months and 7% (6/89) at 1 year. Two patients underwent coil embolization of type II endoleaks at 6.5 months and 2.2 years, respectively. Clinical success was 94% (84/89) at 30 days, 98% (85/87) at 6 months, and 99% (82/83) at 1 year. Early results suggest that properly selected AAA patients can be safely treated using the Altura Endograft System with favorable midterm outcome. Thus, further clinical investigation is warranted to evaluate the role of this device in the treatment of AAA.

Attitudes of elderly Korean patients toward death and dying: an application of Q-methodology.

PubMed

Yeun, Eunja

2005-11-01

The aim of this study was to identify the attitudes of elderly Korean patients toward death and dying using Q-methodology to aid in the development of basic strategies for nursing care of elderly Koreans. Thirty participants at a university hospital sorted 40 selected Q-statements on a nine-point scale. Data analysis identified three types of attitudes toward death and dying in elderly patients in Korea: religion-dependent, science-adherent, and sardonic. Religion-dependent elders are highly dependent upon religion as evidenced by their reply that they would like to rely on God and a minister the most. Science-adherent elders have great affection for life and believe in modern medical advancements. The sardonic elders regard death as the dispensation of nature so there is no need to be afraid of death and dying. This study will contribute to the understanding that nurses and other health professionals have of the perceptions of elderly Koreans about death and dying. Also, the findings may provide the basis for the development of more appropriate strategies to improve death and dying education programs of health professionals.

Residual entanglement and sudden death: A direct connection

NASA Astrophysics Data System (ADS)

de Oliveira, J. G. G.; Peixoto de Faria, J. G.; Nemes, M. C.

2011-11-01

We explore the results of [V. Coffman, et al., Phys. Rev. A 61 (2000) 052306] derived for general tripartite states in a dynamical context. We study a class of physically motivated tripartite systems. We show that whenever entanglement sudden death occurs in one of the partitions residual entanglement will appear. For fourpartite systems however, the appearance of residual entanglement is not conditioned by sudden death of entanglement. We can only say that if sudden death of entanglement occurs in some partition there will certainly be residual entanglement.

Managing the SOS Response for Enhanced CRISPR-Cas-Based Recombineering in E. coli through Transient Inhibition of Host RecA Activity.

PubMed

Moreb, Eirik Adim; Hoover, Benjamin; Yaseen, Adam; Valyasevi, Nisakorn; Roecker, Zoe; Menacho-Melgar, Romel; Lynch, Michael D

2017-12-15

Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes, and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well as mutation rates through induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants. We report an approach to inhibiting the SOS response and RecA activity through the expression of a mutant dominant negative form of RecA, which incorporates into wild type RecA filaments and inhibits activity. Using a plasmid-based system in which Cas9 and recA mutants are coexpressed, we can achieve increased efficiency and consistency of CRISPR-Cas9-mediated selection and recombineering in E. coli, while reducing the induction of the SOS response. To date, this approach has been shown to be independent of recA genotype and host strain lineage. Using this system, we demonstrate increased CRISPR-Cas selection efficacy with over 10 000 guides covering the E. coli chromosome. The use of dominant negative RecA or homologues may be of broad use in bacterial CRISPR-Cas-based genome editing where the SOS pathways are present.

The synthetic purine reversine selectively induces cell death of cancer cells.

PubMed

Piccoli, Marco; Palazzolo, Giacomo; Conforti, Erika; Lamorte, Giuseppe; Papini, Nadia; Creo, Pasquale; Fania, Chiara; Scaringi, Raffaella; Bergante, Sonia; Tringali, Cristina; Roncoroni, Leda; Mazzoleni, Stefania; Doneda, Luisa; Galli, Rossella; Venerando, Bruno; Tettamanti, Guido; Gelfi, Cecilia; Anastasia, Luigi

2012-10-01

The synthetic purine reversine has been shown to possess a dual activity as it promotes the de-differentiation of adult cells, including fibroblasts, into stem-cell-like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti-cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. Copyright © 2012 Wiley Periodicals, Inc.

Changes in and Impact of the Death Review Process in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

PubMed

Miller, Anthony B; Feld, Ronald; Fontana, Robert; Gohagan, John K; Jatoi, Ismail; Lawrence, Walter; Miller, Amy; ProroK, Philip C; Rajput, Ashwani; Sherman, Morris; Welch, Gilbert; Wright, Patrick; Yurgalevitch, Susan; Albertsen, Peter

2015-01-01

Death review was conducted for the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial to avoid the biases associated with causes of death entered on death certificates. An algorithm selected deaths for review. Records on diagnosis and terminal illness were perused in the coordinating center and by the chair of the death review committee (DRC). Identifying information and randomization arm was removed. Three reviewers independently determined the cause of death. Disagreement was resolved at a meeting of the DRC. This process was subsequently simplified. The cause of death was determined by one DRC member and compared to the death certificate. With agreement the case was finalized. When discordant, the records were sent to a second DRC member. If the reviewers agreed, the case was finalized. If not, a third member reviewed. If two of the three reviewers agreed, the case was sent back to the discordant reviewer. If the reviewer remained discordant the case was resolved by a conference call. Of the 4728 death reviews that were completed, the DRC confirmed the death certificate underlying cause for over 90%. Between 5% and 13% of the certified deaths were regarded as indirect causes of death, associated with the treatment of the ascertained cancer; differential for prostate cancer, 11% in the intervention arm and 6% in the control. Without review, between 1% and 6% of the deaths that occurred would not have been assigned to the relevant PLCO cancer. The DRC completed 76% of those requiring review before the process ceased.

Fas-associated Protein with Death Domain (FADD)-independent Recruitment of c-FLIPL to Death Receptor 5*

PubMed Central

Jin, Tai-Guang; Kurakin, Alexei; Benhaga, Nordine; Abe, Karon; Mohseni, Mehrdad; Sandra, Ferry; Song, Keli; Kay, Brian K.; Khosravi-Far, Roya

2010-01-01

Here we show a novel mechanism by which FLICE-like inhibitory protein (c-FLIP) regulates apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and one of its receptors, DR5. c-FLIP is a critical regulator of the TNF family of cytokine receptor signaling. c-FLIP has been postulated to prevent formation of the competent death-inducing signaling complex (DISC) in a ligand-dependent manner, through its interaction with FADD and/or caspase-8. In order to identify regulators of TRAIL function, we used the intracellular death domain (DD) of DR5 as a target to screen a phage-displayed combinatorial peptide library. The DD of DR5 selected from the library a peptide that showed sequence similarity to a stretch of amino acids in the C terminus of c-FLIPL. The phage-displayed peptide selectively interacted with the DD of DR5 in in vitro binding assays. Similarly, full-length c-FLIP (c-FLIPL) and the C-terminal p12 domain of c-FLIP interacted with DR5 both in in vitro pull-down assays and in mammalian cells. This interaction was independent of TRAIL. To the contrary, TRAIL treatment released c-FLIPL from DR5, permitting the recruitment of FADD to the active DR5 signaling complex. By employing FADD-deficient Jurkat cells, we demonstrate that DR5 and c-FLIPL interact in a FADD-independent manner. Moreover, we show that a cellular membrane permeable version of the peptide corresponding to the DR5 binding domain of c-FLIP induces apoptosis in mammalian cells. Taken together, these findings indicate that c-FLIPL interacts with the DD of DR5, thus preventing death signaling by DR5 prior to the formation of an active DISC. Because TRAIL and DR5 are ubiquitously expressed, the interaction of c-FLIPL and DR5 indicates a mechanism by which tumor selective apoptosis can be achieved through protecting normal cells from undergoing death receptor-induced apoptosis. PMID:15485835

'Hints' in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death.

PubMed

Qiu, Shiqiao; Liu, Jing; Xing, Feiyue

2017-04-01

Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections. Intriguingly, other gasdermin family members also share similar N-terminal domains, but they present different cell death programs. Herein, we summarize features and functions of the novel player proteins in cell death, including GSDMD triggering pyroptosis, Gsdma3/GSDMA initiating autophagy/apoptosis and DFNA5 inducing apoptosis/secondary necrosis. The gasdermin N terminus appears to be a novel pore-forming protein. This provides novel insight into the underlying roles and mechanisms of lytic or nonlytic forms of programmed cell death, as well as their potential applications in inflammation-associated diseases.

78 FR 55766 - Submission for Review: Civil Service Retirement System Survivor Annuitant Express Pay Application...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

... Annuitant Express Pay Application for Death Benefits, RI 25-51 AGENCY: U.S. Office of Personnel Management... Service Retirement System Survivor Annuitant Express Pay Application for Death Benefits, RI 25-51. As... widower, based on the report of death, when our records show the decedent elected to provide benefits for...

[WebSurvCa: web-based estimation of death and survival probabilities in a cohort].

PubMed

Clèries, Ramon; Ameijide, Alberto; Buxó, Maria; Vilardell, Mireia; Martínez, José Miguel; Alarcón, Francisco; Cordero, David; Díez-Villanueva, Ana; Yasui, Yutaka; Marcos-Gragera, Rafael; Vilardell, Maria Loreto; Carulla, Marià; Galceran, Jaume; Izquierdo, Ángel; Moreno, Víctor; Borràs, Josep M

2018-01-19

Relative survival has been used as a measure of the temporal evolution of the excess risk of death of a cohort of patients diagnosed with cancer, taking into account the mortality of a reference population. Once the excess risk of death has been estimated, three probabilities can be computed at time T: 1) the crude probability of death associated with the cause of initial diagnosis (disease under study), 2) the crude probability of death associated with other causes, and 3) the probability of absolute survival in the cohort at time T. This paper presents the WebSurvCa application (https://shiny.snpstats.net/WebSurvCa/), whereby hospital-based and population-based cancer registries and registries of other diseases can estimate such probabilities in their cohorts by selecting the mortality of the relevant region (reference population). Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Relationship between using conceptual comprehension of academic material and thinking abstractly about global life issues.

PubMed

Westman, A S; Kamoo, R L

1990-04-01

The study explored whether more frequent use of conceptual comprehension of academic material generalized to greater use of abstract thinking about global life issues, such as death, goal in life, marriage, AIDS, etc. Undergraduate and graduate students (28 men and 61 women) voluntarily completed a questionnaire which assessed their conceptualizations using three indices. These were an intelligence scale and two learning style indices, namely, Deep Processing and Elaborative Processing of R. R. Schmeck. Also assessed were their levels of abstract thinking about Death Issues and about Other Real Life Issues, and their Denial of Death and their Denial of Dying. All three indices of conceptualization correlated with thinking more abstractly about Other Real Life Issues, but only Elaborative Processing correlated with thinking more abstractly about Death Issues. None of the three indices correlated with Denial of Death or Denial of Dying. It appears conceptualization skills were selectively generalized.

Functional mechanotransduction is required for cisplatin-induced hair cell death in the zebrafish lateral line

PubMed Central

Thomas, Andrew J.; Hailey, Dale W.; Stawicki, Tamara M.; Wu, Patricia; Coffin, Allison B.; Rubel, Edwin W.; Raible, David W.; Simon, Julian A.; Ou, Henry C.

2013-01-01

Cisplatin, one of the most commonly used anti-cancer drugs, is known to cause inner ear hair cell damage and hearing loss. Despite much investigation into mechanisms of cisplatin-induced hair cell death, little is known about the mechanism whereby cisplatin is selectively toxic to hair cells. Using hair cells of the zebrafish lateral line, we found that chemical inhibition of mechanotransduction with quinine and EGTA protected against cisplatin-induced hair cell death. Furthermore, we found that the zebrafish mutants mariner (myo7aa) and sputnik (cad23) that lack functional mechanotransduction were resistant to cisplatin-induced hair cell death. Using a fluorescent analogue of cisplatin, we found that chemical or genetic inhibition of mechanotransduction prevented its uptake. These findings demonstrate that cisplatin-induced hair cell death is dependent on functional mechanotransduction in the zebrafish lateral line. PMID:23467357

Causes of Death of Adults and Elderly and Healthcare-seeking before Death in Rural Bangladesh

PubMed Central

Chowdhury, Hafizur Rahman; Bhuiyan, Monirul Alam; Streatfield, Peter Kim

2010-01-01

The health system of a country needs to be adjusted to patterns of morbidity and mortality to mitigate the income-erosion consequences of prolonged ill-health and premature death of adults. Population-based data on mortality by cause are a key to modifying the health system. However, these data are scarce, particularly for rural populations in developing countries. The objectives of this study were to determine the burdens of health due to major causes of death obtained from verbal autopsy of adults and the elderly and their healthcare-seeking patterns before death in a well-defined rural population. There were 2,397 deaths—613 were among adults aged 15-59 years and 1,784 among the elderly aged 60+ years—during 2003-2004 in the health and demographic surveillance area in Matlab, a rural area of Bangladesh. Trained interviewers interviewed close relatives of the deceased using a structured verbal-autopsy questionnaire to record signs and symptoms of diseases/conditions that led to death and medical consultations before death. Two physicians independently assigned the underlying causes of deaths with disagreements resolved by a third physician. The physicians were able to assign a specific cause in 91% of the cases. Rates and proportions were used for estimating the burden of diseases by cause. Of all deaths of adults and the elderly, communicable diseases accounted for 18% and non-communicable diseases for 66%, with the proportion of non-communicable diseases increasing with age. Leading non-communicable diseases were diseases of the circulatory system (35%), neoplasms (11%), diseases of the respiratory system (10%), diseases of the digestive system (6%), and endocrine and metabolic disorders (6%), all of which accounted for 68% of deaths. Injury and other external causes accounted for another 5% of the deaths. During terminal illness, 31% of the adults and 25% of the elderly sought treatment from medical doctors, and 14% of the adults and 4% of the elderly died in healthcare facilities. The findings suggest that the health managers and policy-makers of Bangladesh should recognize the importance of prevention and management of chronic diseases and place it on the health agenda for rural people. PMID:20941904

LACE+ index: extension of a validated index to predict early death or urgent readmission after hospital discharge using administrative data

PubMed Central

van Walraven, Carl; Wong, Jenna; Forster, Alan J

2012-01-01

Background Death or urgent readmission after hospital discharge is a common adverse event that can be used to compare outcomes of care between institutions. To accurately adjust for risk and to allow for interhospital comparisons of readmission rates, we used administrative data to derive and internally validate an extension of the LACE index, a previously validated index for 30-day death or urgent readmission. Methods We randomly selected 500 000 medical and surgical patients discharged to the community from any Ontario hospital between 1 April 2003 and 31 March 2009. We derived a logistic regression model on 250 000 randomly selected patients from this group and modified the final model into an index scoring system, the LACE+ index. We internally validated the LACE+ index using data from the remaining 250 000 patients and compared its performance with that of the original LACE index. Results Within 30 days of discharge to the community, 33 825 (6.8%) of the patients had died or had been urgently readmitted. In addition to the variables included in the LACE index (length of stay in hospital [L], acuity of admission [A], comorbidity [C] and emergency department utilization in the 6 months before admission [E]), the LACE+ index incorporated patient age and sex, teaching status of the discharge hospital, acute diagnoses and procedures performed during the index admission, number of days on alternative level of care during the index admission, and number of elective and urgent admissions to hospital in the year before the index admission. The LACE+ index was highly discriminative (C statistic 0.771, 95% confidence interval 0.767–0.775), was well calibrated across most of its range of scores and had a model performance that exceeded that of the LACE index. Interpretation The LACE+ index can be used to predict the risk of postdischarge death or urgent readmission on the basis of administrative data for the Ontario population. Its performance exceeds that of the LACE index, and it allows analysts to accurately estimate the risk of important postdischarge outcomes. PMID:23696773

Skin lesion computational diagnosis of dermoscopic images: Ensemble models based on input feature manipulation.

PubMed

Oliveira, Roberta B; Pereira, Aledir S; Tavares, João Manuel R S

2017-10-01

The number of deaths worldwide due to melanoma has risen in recent times, in part because melanoma is the most aggressive type of skin cancer. Computational systems have been developed to assist dermatologists in early diagnosis of skin cancer, or even to monitor skin lesions. However, there still remains a challenge to improve classifiers for the diagnosis of such skin lesions. The main objective of this article is to evaluate different ensemble classification models based on input feature manipulation to diagnose skin lesions. Input feature manipulation processes are based on feature subset selections from shape properties, colour variation and texture analysis to generate diversity for the ensemble models. Three subset selection models are presented here: (1) a subset selection model based on specific feature groups, (2) a correlation-based subset selection model, and (3) a subset selection model based on feature selection algorithms. Each ensemble classification model is generated using an optimum-path forest classifier and integrated with a majority voting strategy. The proposed models were applied on a set of 1104 dermoscopic images using a cross-validation procedure. The best results were obtained by the first ensemble classification model that generates a feature subset ensemble based on specific feature groups. The skin lesion diagnosis computational system achieved 94.3% accuracy, 91.8% sensitivity and 96.7% specificity. The input feature manipulation process based on specific feature subsets generated the greatest diversity for the ensemble classification model with very promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

Rates and Correlates of Undetermined Deaths among African Americans: Results from the National Violent Death Reporting System

ERIC Educational Resources Information Center

Huguet, Nathalie; Kaplan, Mark S.; McFarland, Bentson H.

2012-01-01

Little is known about the factors associated with undetermined death classifications among African Americans. In this study, the rates of undetermined deaths were assessed, the prevalence of missing information was estimated, and whether the circumstances preceding death differ by race were examined. Data were derived from the 2005-2008 National…

Completeness and reliability of mortality data in Viet Nam: Implications for the national routine health management information system.

PubMed

Hong, Tran Thi; Phuong Hoa, Nguyen; Walker, Sue M; Hill, Peter S; Rao, Chalapati

2018-01-01

Mortality statistics form a crucial component of national Health Management Information Systems (HMIS). However, there are limitations in the availability and quality of mortality data at national level in Viet Nam. This study assessed the completeness of recorded deaths and the reliability of recorded causes of death (COD) in the A6 death registers in the national routine HMIS in Viet Nam. 1477 identified deaths in 2014 were reviewed in two provinces. A capture-recapture method was applied to assess the completeness of the A6 death registers. 1365 household verbal autopsy (VA) interviews were successfully conducted, and these were reviewed by physicians who assigned multiple and underlying cause of death (UCOD). These UCODs from VA were then compared with the CODs recorded in the A6 death registers, using kappa scores to assess the reliability of the A6 death register diagnoses. The overall completeness of the A6 death registers in the two provinces was 89.3% (95%CI: 87.8-90.8). No COD recorded in the A6 death registers demonstrated good reliability. There is very low reliability in recording of cardiovascular deaths (kappa for stroke = 0.47 and kappa for ischaemic heart diseases = 0.42) and diabetes (kappa = 0.33). The reporting of deaths due to road traffic accidents, HIV and some cancers are at a moderate level of reliability with kappa scores ranging between 0.57-0.69 (p<0.01). VA methods identify more specific COD than the A6 death registers, and also allow identification of multiple CODs. The study results suggest that data completeness in HMIS A6 death registers in the study sample of communes was relatively high (nearly 90%), but triangulation with death records from other sources would improve the completeness of this system. Further, there is an urgent need to enhance the reliability of COD recorded in the A6 death registers, for which VA methods could be effective. Focussed consultation among stakeholders is needed to develop a suitable mechanism and process for integrating VA methods into the national routine HMIS A6 death registers in Viet Nam.

Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

PubMed

Mendez, L C; Moraes, F Y; Fernandes, G Dos S; Weltman, E

2018-01-01

Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Thousands of cancer patients requiring radiotherapy do not have access to this treatment in the Brazilian public health system. The shortage of radiotherapy has a significant detrimental effect on cancer survival; over 5000 deaths would probably be prevented in the most common cancer types if radiotherapy access was universal. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Comparative study of control selection in a national population-based case-control study: Estimating risk of smoking on cancer deaths in Chinese men.

PubMed

Jiang, Jingmei; Liu, Boqi; Nasca, Philip C; Han, Wei; Zou, Xiaonong; Zeng, Xianjia; Tian, Xiaobing; Wu, Yanping; Zhao, Ping; Li, Junyao

2009-10-28

To assess the validation of a novel control selection design by comparing the consistency between the new design and a routine design in a large case-control study that was incorporated into a nationwide mortality survey in China. A nationwide mortality study was conducted during 1989-1991. Surviving spouses or other relatives of all adults who died during 1986-1988 provided detailed information about their own as well as the deceased person's smoking history. In this study, 130,079 males who died of various smoking-related cancers at age 35 or over were taken as cases, while 103,248 male surviving spouses (same age range with cases) of women who died during the same period and 49,331 males who died from causes other than those related to smoking were used as control group 1 and control group 2, respectively. Consistency in the results when comparing cases with each of the control groups was assessed. Consistency in the results was observed in the analyses using different control groups although cancer deaths varied with region and age. Equivalence could be ascertained using a 15% criterion in most cancer deaths which had high death rates in urban areas, but they were uncertain for most cancers in rural areas irrespective of whether the hypothesis testing showed significant differences or not. Sex-matched living spouse control design as an alternative control selection for a case-control study is valid and feasible, and the basic principles of the equivalence study are also supported by epidemiological survey data.

The national review of asthma deaths: what did we learn and what needs to change?

PubMed Central

2015-01-01

Key points The 2014 UK National Review of Asthma Deaths identified potentially preventable factors in two-thirds of the medical records of cases scrutinised 45% of people who died from asthma did not call for or receive medical assistance in their final fatal attack Overall asthma management, acute and chronic, in primary and secondary care was judged to be good in less than one-fifth of those who died There was a failure by doctors and nurses to identify and act on risk factors for asthma attacks and asthma death The rationale for diagnosing asthma was not evident in a considerable number of cases, and there were inaccuracies related to the completion of medical certificates of the cause of death in over half of the cases considered for the UK National Review of Asthma Deaths Educational aims To increase awareness of some of the findings of the recent UK National Review of Asthma Deaths and previous similar studies To emphasise the need for accurate diagnosis of asthma, and of the requirements for completion of medical certificates of the cause of death To consider areas for improving asthma care and prevention of attacks and avoidable deaths Summary Despite the development and publication of evidence-based asthma guidelines nearly three decades ago, potentially preventable factors are repeatedly identified in studies of the care provided for patients who die from asthma. The UK National Review of Asthma Deaths (NRAD), a confidential enquiry, was no exception: major preventable factors were identified in two-thirds of asthma deaths. Most of these factors, such as inappropriate prescription and failure to provide patients with personal asthma action plans (PAAPs), could possibly have been prevented had asthma guidelines been implemented. NRAD involved in-depth scrutiny by clinicians of the asthma care for 276 people who were classified with asthma as the underlying cause of death in real-life. A striking finding was that a third of these patients did not actually die from asthma, and many had no recorded rationale for an asthma diagnosis. The apparent complacency with respect to asthma care, highlighted in NRAD, serves as a wake-up call for health professionals, patients and their carers to take asthma more seriously. Based on the NRAD evidence, the report made 19 recommendations for change. The author has selected six areas related to the NRAD findings for discussion and provides suggestions for change in the provision of asthma care. The six areas are: systems for provision and optimisation of asthma care, diagnosis, identifying risk, implementation of guidelines, improved patient education and self-management, and improved quality of completion of medical certificates of the cause of death. PMID:26306100

Death Preparation of Chinese Rural Elders.

PubMed

Liu, Yanping; van Schalkwyk, Gertina J

2018-05-14

In this qualitative study, we explored how Chinese rural elders narrate death-related issues and death preparation. Adopting a phenomenological approach, we interviewed 14 participants regarding the particular actions they employ to prepare for death. The findings revealed a death preparation system for rural Chinese elders that is instrumental in how they converse about death, wish for a good death, make objects and symbols, and anticipate an afterlife as a worshiped ancestor rather than a wandering ghost. Family and family honour provide the context for death preparation. We discuss implications and the need for the death preparation education of younger generations.

Is cancer a good way to die? A population-based survey among middle-aged and older adults in the United Kingdom.

PubMed

Vrinten, Charlotte; Wardle, Jane

2016-03-01

Despite improved outcomes, cancer remains widely feared, often because of its association with a long and protracted death as opposed to the quick death that people associate with that other common cause of adult mortality: heart disease. Former editor-in-chief of the BMJ Richard Smith's view that 'cancer is the best way to die' therefore attracted much criticism. We examined middle-aged and older adults' agreement with this view and compared their attitudes towards dying from cancer versus heart disease in terms of which was a good death. This study was part of an online survey (February 2015) in a United Kingdom (UK) population sample of 50- to 70-year olds (n = 391), with sampling quotas for gender and education. Five characteristics of 'a good death' were selected from the end-of-life literature. Respondents were asked to rate the importance of each characteristic for their own death to ensure their relevance to a population sample and the likelihood of each for death from cancer and heart disease. We also asked whether they agreed with Smith's view. At least 95% of respondents considered the selected five characteristics important for their own death. Death from cancer was rated as more likely to provide control over what happens (p < 0.001), control over pain and other symptoms (p < 0.01), time to settle affairs (p < 0.001), and time to say goodbye to loved ones (p < 0.001) compared with death from heart disease, but there were no differences in expectation of living independently until death (p > 0.05). Almost half (40%) agreed that cancer is 'the best way to die', with no differences by age (p = 0.40), gender (p = 0.85), or education (p = 0.27). Despite the media commotion, a surprisingly high proportion of middle-aged and older adults viewed cancer as 'the best way to die' and rated cancer death as better than heart disease. Given that one in two of us are likely to be diagnosed with cancer, conversations about a good death from cancer may in a small way mitigate fear of cancer. Future research could explore variations by type of cancer or heart disease and by previous experience of these illnesses in others. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

PubMed

Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

2012-07-01

Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death.

[Application of artificial neural networks in forecasting the number of circulatory system diseases death toll].

PubMed

Zhang, Ying; Shao, Yi; Shang, Kezheng; Wang, Shigong; Wang, Jinyan

2014-09-01

Set up the model of forecasting the number of circulatorys death toll based on back-propagation (BP) artificial neural networks discuss the relationship between the circulatory system diseases death toll meteorological factors and ambient air pollution. The data of tem deaths, meteorological factors, and ambient air pollution within the m 2004 to 2009 in Nanjing were collected. On the basis of analyzing the ficient between CSDDT meteorological factors and ambient air pollution, leutral network model of CSDDT was built for 2004 - 2008 based on factors and ambient air pollution within the same time, and the data of 2009 est the predictive power of the model. There was a closely system diseases relationship between meteorological factors, ambient air pollution and the circulatory system diseases death toll. The ANN model structure was 17 -16 -1, 17 input notes, 16 hidden notes and 1 output note. The training precision was 0. 005 and the final error was 0. 004 999 42 after 487 training steps. The results of forecast show that predict accuracy over 78. 62%. This method is easy to be finished with smaller error, and higher ability on circulatory system death toll on independent prediction, which can provide a new method for forecasting medical-meteorological forecast and have the value of further research.

Causes of mortality in an African city.

PubMed

Ayeni, O

1980-01-01

Registered deaths from the vital statistics registration system of Lagos City, a system that was judged to be 60% complete, were analysed for the year 1977. Nearly 40% of total registered deaths were from infections, parasitic diseases and motor vehicle accidents. Of the reported deaths, 17.3% were from ill-defined conditions. Deaths from neoplasms, diseases of the nervous and sense organs, diseases of the digestive and genitourinary systems as well as those from congenital anomalies are relatively less frequent. Maternal mortality appears to be very high. The age pattern of mortality is different from that in the developed countries, a high proportion of the deaths in Lagos City being those of children aged under 5 years. Infant mortality is dominated by perinatal causes which constituted a huge 38.4% of deaths of infants under 1 year, the other important causes being dysentery and diarrhoea, pneumonia and tetanus. Among adults, death from motor vehicles accidents is the most important cause accounting for more than 26% of deaths in the age group 15 years and above. Other important causes of adult deaths are cerebrovascular disease, hypertensive disease, heart disease, pneumonia, dysentery and diarrhoea and complications of pregnancy. Well organized health services stressing antenatal care, preventive and health education services are needed to effect a reduction in mortality and bring about a general improvement in the health of the people.

Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths

PubMed Central

Mehboob, Riffat

2017-01-01

Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life. PMID:28348544

Substance P/Neurokinin 1 and Trigeminal System: A Possible Link to the Pathogenesis in Sudden Perinatal Deaths.

PubMed

Mehboob, Riffat

2017-01-01

Sudden demise of a healthy fetus or a neonate is a very tragic episode in the life of parents. These deaths have been a mystery since ages but still remain unexplained. This review proposes the involvement of trigeminal nerve, neurotransmitter substance P (SP), and its receptor neurokinin 1 (NK-1R) in regulation of cardiorespiratory control in fetuses and newborns. Anomalies and immaturity of neuroregulatory systems such as trigeminal system in medulla oblongata of brainstem may provide a possible mechanism of sudden perinatal deaths. Vulnerable infants are born with respiratory center immaturity which in combination with any stressor such as cold, hypoxia, and smoking may lead to cessation of breathing and ventilatory response. SP/NK-1R may be involved in regulating the ventilatory control in neonates while it is decreased in fetal and adult life in humans, and any alterations from these may lead to irreversible sleep apnea and fatal breathing, ultimately sudden death. This review summarizes the studies performed to highlight the expression of SP or NK-1R in sudden perinatal deaths and proposes the involvement of trigeminal ganglion along with its nerve and SP/NK-1R expression alteration as one of the possible pathophysiological underlying mechanism. However, further studies are required to explore the role of SP, NK-1R, and trigeminal system in the pathogenesis of sudden infant deaths, sudden intrauterine deaths, stillbirths, and sudden deaths later in human life.

Long-term mortality study of steelworkers. IX. Mortality patterns among sheet and tin mill workers.

PubMed

Mazumdar, S; Lerer, T; Redmond, C K

1975-12-01

As a result of findings of an earlier report in this series, this study examines the updated cause-specific mortality of men employed in the sheet and tin mill areas of the steel industry. In order to investigate possible relationships between occupational responsibilities or exposures and mortality from specific causes, the sheet and tin mills have been subdivided into 13 mutually exclusive work areas. Detailed analysis is limited primarily to white workers due to the small number of nonwhites in these areas. The most important observations are: 1. Increased overall mortality appears for men employed in 1953 in the sheet finishing and shipping area, confirming the findings of Lloyd, et al. The earlier observation of a significant excess in deaths from vascular lesions of the central nervous system does not hold over time. The previously noted excess for this cause may be related to selective factors or an extreme chance observation. The excess in mortality from all causes of death, which occurs over several disease categories, may not be a result of occupational exposures, but rather some selectivity. 2. Significant excesses in mortality from arteriosclerotic heart disease are noted among men employed in batch pickling and sheet dryer operations, which is in agreement with the earlier findings. Increased risks of dying from hypertensive heart disease are seen in the coating area. 3. Cancer of the lymphatic and hematopoietic tissues is found to be a significant source of excess mortality for workers in the heat treating and forging and tin finishing and shipping work areas. 4. Steelworkers employed in the annealing-normalizing work area show an excess in deaths from nonmalignant respiratory diseases, primarily pneumonia. Further study in these areas should attempt to investigate whether factors in the work environment may be responsible for the observed excess mortalities. More specifically, work should be done to find out whether men employed in heat treating and forging and tin finishing and shipping work in close proximity to chemicals or radiation exposure and whether workers employed in the annealing-normalizing area are exposed to any kind of oil, vapor, or chemical which might be irritating or infectious to the respiratory system. A similar analysis for men working in the batch pickling and sheet dryers and coating areas would also be worthwhile. The main emphasis of any future study should lie upon investigating whether the observed excess mortalities are due to any environmental factor, selection for health, or random fluctuation.

Mortality in Iraq Associated with the 2003–2011 War and Occupation: Findings from a National Cluster Sample Survey by the University Collaborative Iraq Mortality Study

PubMed Central

Hagopian, Amy; Flaxman, Abraham D.; Takaro, Tim K.; Esa Al Shatari, Sahar A.; Rajaratnam, Julie; Becker, Stan; Levin-Rector, Alison; Galway, Lindsay; Hadi Al-Yasseri, Berq J.; Weiss, William M.; Murray, Christopher J.; Burnham, Gilbert

2013-01-01

Background Previous estimates of mortality in Iraq attributable to the 2003 invasion have been heterogeneous and controversial, and none were produced after 2006. The purpose of this research was to estimate direct and indirect deaths attributable to the war in Iraq between 2003 and 2011. Methods and Findings We conducted a survey of 2,000 randomly selected households throughout Iraq, using a two-stage cluster sampling method to ensure the sample of households was nationally representative. We asked every household head about births and deaths since 2001, and all household adults about mortality among their siblings. We used secondary data sources to correct for out-migration. From March 1, 2003, to June 30, 2011, the crude death rate in Iraq was 4.55 per 1,000 person-years (95% uncertainty interval 3.74–5.27), more than 0.5 times higher than the death rate during the 26-mo period preceding the war, resulting in approximately 405,000 (95% uncertainty interval 48,000–751,000) excess deaths attributable to the conflict. Among adults, the risk of death rose 0.7 times higher for women and 2.9 times higher for men between the pre-war period (January 1, 2001, to February 28, 2003) and the peak of the war (2005–2006). We estimate that more than 60% of excess deaths were directly attributable to violence, with the rest associated with the collapse of infrastructure and other indirect, but war-related, causes. We used secondary sources to estimate rates of death among emigrants. Those estimates suggest we missed at least 55,000 deaths that would have been reported by households had the households remained behind in Iraq, but which instead had migrated away. Only 24 households refused to participate in the study. An additional five households were not interviewed because of hostile or threatening behavior, for a 98.55% response rate. The reliance on outdated census data and the long recall period required of participants are limitations of our study. Conclusions Beyond expected rates, most mortality increases in Iraq can be attributed to direct violence, but about a third are attributable to indirect causes (such as from failures of health, sanitation, transportation, communication, and other systems). Approximately a half million deaths in Iraq could be attributable to the war. Please see later in the article for the Editors' Summary PMID:24143140

Mortality in Iraq associated with the 2003-2011 war and occupation: findings from a national cluster sample survey by the university collaborative Iraq Mortality Study.

PubMed

Hagopian, Amy; Flaxman, Abraham D; Takaro, Tim K; Esa Al Shatari, Sahar A; Rajaratnam, Julie; Becker, Stan; Levin-Rector, Alison; Galway, Lindsay; Hadi Al-Yasseri, Berq J; Weiss, William M; Murray, Christopher J; Burnham, Gilbert

2013-10-01

Previous estimates of mortality in Iraq attributable to the 2003 invasion have been heterogeneous and controversial, and none were produced after 2006. The purpose of this research was to estimate direct and indirect deaths attributable to the war in Iraq between 2003 and 2011. We conducted a survey of 2,000 randomly selected households throughout Iraq, using a two-stage cluster sampling method to ensure the sample of households was nationally representative. We asked every household head about births and deaths since 2001, and all household adults about mortality among their siblings. We used secondary data sources to correct for out-migration. From March 1, 2003, to June 30, 2011, the crude death rate in Iraq was 4.55 per 1,000 person-years (95% uncertainty interval 3.74-5.27), more than 0.5 times higher than the death rate during the 26-mo period preceding the war, resulting in approximately 405,000 (95% uncertainty interval 48,000-751,000) excess deaths attributable to the conflict. Among adults, the risk of death rose 0.7 times higher for women and 2.9 times higher for men between the pre-war period (January 1, 2001, to February 28, 2003) and the peak of the war (2005-2006). We estimate that more than 60% of excess deaths were directly attributable to violence, with the rest associated with the collapse of infrastructure and other indirect, but war-related, causes. We used secondary sources to estimate rates of death among emigrants. Those estimates suggest we missed at least 55,000 deaths that would have been reported by households had the households remained behind in Iraq, but which instead had migrated away. Only 24 households refused to participate in the study. An additional five households were not interviewed because of hostile or threatening behavior, for a 98.55% response rate. The reliance on outdated census data and the long recall period required of participants are limitations of our study. Beyond expected rates, most mortality increases in Iraq can be attributed to direct violence, but about a third are attributable to indirect causes (such as from failures of health, sanitation, transportation, communication, and other systems). Approximately a half million deaths in Iraq could be attributable to the war. Please see later in the article for the Editors' Summary.

Use of primary diagnosis during hospitalization in the Unified Health System (Sistema Único de Saúde) to qualify information regarding the underlying cause of natural deaths among the elderly.

PubMed

Cascão, Angela Maria; Jorge, Maria Helena Prado de Mello; Costa, Antonio José Leal; Kale, Pauline Lorena

2016-01-01

Ill-defined causes of death are common among the elderly owing to the high frequency of comorbidities and, consequently, to the difficulty in defining the underlying cause of death. To analyze the validity and reliability of the "primary diagnosis" in hospitalization to recover the information on the underlying cause of death in natural deaths among the elderly whose deaths were originally assigned to "ill-defined cause" in their Death Certificate. The hospitalizations occurred in the state of Rio de Janeiro, in 2006. The databases obtained in the Information Systems on Mortality and Hospitalization were probabilistically linked. The following data were calculated for hospitalizations of the elderly that evolved into deaths with a natural cause: concordance percentages, Kappa coefficient, sensitivity, specificity, and the positive predictive value of the primary diagnosis. Deaths related to "ill-defined causes" were assigned to a new cause, which was defined based on the primary diagnosis. The reliability of the primary diagnosis was good, according to the total percentage of consistency (50.2%), and fair, according to the Kappa coefficient (k = 0.4; p < 0.0001). Diseases related to the circulatory system and neoplasia occurred with the highest frequency among the deaths and the hospitalizations and presented a higher consistency of positive predictive values per chapter and grouping of the International Classification of Diseases. The recovery of the information on the primary cause occurred in 22.6% of the deaths with ill-defined causes (n = 14). The methodology developed and applied for the recovery of the information on the natural cause of death among the elderly in this study had the advantage of effectiveness and the reduction of costs compared to an investigation of the death that is recommended in situations of non-linked and low positive predictive values. Monitoring the mortality profile by the cause of death is necessary to periodically update the predictive values.

Causes of death in the Taabo health and demographic surveillance system, Côte d'Ivoire, from 2009 to 2011.

PubMed

Koné, Siaka; Fürst, Thomas; Jaeger, Fabienne N; Esso, Emmanuel L J C; Baïkoro, Nahoua; Kouadio, Kouamé A; Adiossan, Lukas G; Zouzou, Fabien; Boti, Louis I; Tanner, Marcel; Utzinger, Jürg; Bonfoh, Bassirou; Dao, Daouda; N'Goran, Eliézer K

2015-01-01

Current vital statistics from governmental institutions in Côte d'Ivoire are incomplete. This problem is particularly notable for remote rural areas that have limited access to the health system. To record all deaths from 2009 to 2011 and to identify the leading causes of death in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire. Deaths recorded in the first 3 years of operation of the Taabo HDSS were investigated by verbal autopsy (VA), using the InterVA-4 model. InterVA-4 is based on the World Health Organization 2012 VA tool in terms of input indicators and categories of causes of death. Overall, 948 deaths were recorded, of which 236 (24.9%) had incomplete VA data. Among the 712 deaths analyzed, communicable diseases represented the leading causes (58.9%), with most deaths attributed to malaria (n=129), acute respiratory tract infections (n=110), HIV/AIDS (n=80), and pulmonary tuberculosis (n=46). Non-communicable diseases accounted for 18.9% of the deaths and included mainly acute abdomen (n=38), unspecified cardiac diseases (n=15), and digestive neoplasms (n=13). Maternal and neonatal conditions accounted for 8.3% of deaths, primarily pneumonia (n=19) and birth asphyxia (n=16) in newborns. Among the 3.8% of deaths linked to trauma and injury, the main causes were assault (n=6), accidental drowning (n=4), contact with venomous plants/animals (n=4), and traffic-related accidents (n=4). No clear causes were determined in 10.0% of the analyzed deaths. Communicable diseases remain the predominant cause of death in rural Côte d'Ivoire. Based on these findings, measures are now being implemented in the Taabo HDSS. It will be interesting to monitor patterns of mortality and causes of death in the face of rapid demographic and epidemiological transitions in this part of West Africa.

A SURVEY OF DEATH ADJUSTMENT IN THE INDIAN SUBCONTINENT.

PubMed

Hossain, Mohammad Samir; Irfan, Muhammad; Balhara, Yatan Pal Singh; Giasuddin, Noor Ahmed; Sultana, Syeda Naheed

2015-01-01

The Death Adjustment Hypothesis (DAH) postulates two key themes. Its first part postulates that death should not be considered the end of existence and the second part emphasizes that the belief in immortal pattern of human existence can only be adopted in a morally rich life with the attitude towards morality and materialism balanced mutually. We wanted to explore Death Adjustment in the Indian subcontinent and the differences among, Indians, Pakistanis and Bangladeshis. We also wanted to find the relationship between death adjustment (i.e., adaptation to death), materialistic thoughts and death adjustment thoughts. This was a cross-sectional study, conducted from May 2010 to June 2013. Using a purposive sampling strategy, a sample of 296 participants from the Indian subcontinent [Pakistan (n=100), Bangladesh (n=98) and India (n=98)] was selected. Multidimensional Fear of Death Scale (MFODS) was used to measure death adjustment. The rest of the variables were measured using lists of respective thoughts, described in elaborated DAH. Analyses were carried out using SPSSv13. The mean death adjustment score for Pakistani, Indian and Bangaldeshi population were 115.26 +/- 26.4, 125.87 +/- 24.3 and 114.91 +/- 21.2, respectively. Death adjustment was better with older age (r=0.20) and with lower scores on materialistic thoughts (r = -0.26). However, this was a weak relation. The three nationalities were compared with each other by using Analysis of variance. Death adjustment thoughts and death adjustment were significantly different when Indians were compared with Bangladeshis (p=0.00) and Pakistanis (p=0.006) but comparison between Bangladeshis and Pakistanis showed no significant difference. Subjects with lesser materialistic thoughts showed better death adjustment. There are differences between Muslims and non-Muslims in adjusting to death.

How to justify avoidance of communications related to death anxiety in the health care system.

PubMed

Sariyar, Murat

2015-08-01

It might seem obvious that dealing with death anxiety in the health care system is desirable. Hence, there are either voices that demand more research on how this openness can be fostered or those who consider this topic unworthy of further investigations because of its triviality. The idea behind both deficient perspectives is that the health care system as a communication system can assume the position of a second-order observer who can account for his deficits. However, in terms of Luhmannian systems theory, external perturbations cannot force a functional system to reflect and change the structure of his communications in a certain way. The health care system as a communication system cannot do more than integrating the topic of death anxiety in terms of its functional perpetuation. For example, in hospitals, neither health care staff nor external counselors are able to address existential issues without being affected by functional and structural requirements of the hospital. We present an outline for the justification of the avoidance of death-anxiety related talk in the health care system by reference to systems theory and existential philosophy.

[Study on smoking-attributed mortality by using all causes of death surveillance system in Tianjin].

PubMed

Jiang, Guohong; Zhang, Hui; Li, Wei; Wang, Dezheng; Xu, Zhongliang; Song, Guide; Zhang, Ying; Shen, Chengfeng; Zheng, Wenlong; Xue, Xiaodan; Shen, Wenda

2016-03-01

To understand the smoking-attributed mortality by inclusion of smoking information into all causes of death surveillance. Since 2010, the information about smoking status, smoking history and the number of cigarettes smoked daily had been added in death surveillance system. The measures of training, supervision, check, sampling survey and telephone verifying were taken to increase death reporting rate and reduce data missing rate and underreporting rate. Multivariate logistic regression analysis was conducted to identify risk factors for smoking-attributed mortality. During the study period (2010-2014), the annual death reporting rates ranged from 6.5‰ to 7.0‰. The reporting rates of smoking status, smoking history and the number of cigarettes smoked daily were 95.53%, 98.63% and 98.58%, respectively. Compared with the nonsmokers, the RR of males was 1.38 (1.33-1.43) for all causes of death and 3.07 (2.91-3.24) for lung cancer due to smoking, the RR of females was 1.46 (1.39-1.54) for all causes of death and 4.07 (3.81-4.35) for lung cancer due to smoking, respectively. The study of smoking attributed mortality can be developed with less investment by using the stable and effective all causes of death surveillance system in Tianjin.

Matrix metalloproteinase-3 causes dopaminergic neuronal death through Nox1-regenerated oxidative stress.

PubMed

Choi, Dong-Hee; Kim, Ji-Hye; Seo, Joo-Ha; Lee, Jongmin; Choi, Wahn Soo; Kim, Yoon-Seong

2014-01-01

In the present study we investigated the interplay between matrix metalloproteinase 3 (MMP3) and NADPH oxidase 1 (Nox1) in the process of dopamine (DA) neuronal death. We found that MMP3 activation causes the induction of Nox1 via mitochondrial reactive oxygen species (ROS) production and subsequently Rac1 activation, eventually leading to Nox1-derived superoxide generation in a rat DA neuronal N27 cells exposed to 6-OHDA. While a MMP3 inhibitor, NNGH, largely attenuated mitochondrial ROS and subsequent Nox1 induction, both apocynin, a putative Nox inhibitor and GKT137831, a Nox1 selective inhibitor failed to reduce 6-OHDA-induced mitochondrial ROS. However, both inhibitors for MMP3 and Nox1 similarly attenuated 6-OHDA-induced N27 cell death. RNAi-mediated selective inhibition of MMP3 or Nox1 showed that knockdown of either MMP3 or Nox1 significantly reduced 6-OHDA-induced ROS generation in N27 cells. While 6-OHDA-induced Nox1 was abolished by MMP3 knockdown, Nox1 knockdown did not alter MMP3 expression. Direct overexpression of autoactivated MMP3 (actMMP3) in N27 cells or in rat substantia nigra (SN) increased expression of Nox1. Selective knockdown of Nox1 in the SN achieved by adeno-associated virus-mediated overexpression of Nox1-specific shRNA largely attenuated the actMMP3-mediated dopaminergic neuronal loss. Furthermore, Nox1 expression was significantly attenuated in Mmp3 null mice treated with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Together we established novel molecular mechanisms underlying oxidative stress-mediated dopaminergic neuronal death in which MMP3 activation is a key upstream event that leads to mitochondrial ROS, Nox1 induction and eventual dopaminergic neuronal death. Our findings may lead to the development of novel therapeutic approach.

alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

PubMed

Tomasetti, M; Strafella, E; Staffolani, S; Santarelli, L; Neuzil, J; Guerrieri, R

2010-04-13

A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

Aryl- and alkyl-phosphorus-containing flame retardants induced mitochondrial impairment and cell death in Chinese hamster ovary (CHO-k1) cells.

PubMed

Huang, Chao; Li, Na; Yuan, Shengwu; Ji, Xiaoya; Ma, Mei; Rao, Kaifeng; Wang, Zijian

2017-11-01

Phosphorus-containing flame retardants (PFRs) are increasingly in demand worldwide as replacements for brominated flame retardants (BFRs), but insufficient available toxicological information on PFRs makes assessing their health risks challenging. Mitochondria are important targets of various environmental pollutants, and mitochondrial dysfunction may lead to many common diseases. In the present study, mitochondria impairment-related endpoints were measured by a high content screening (HCS) assay for 11 selected non-halogen PFRs in Chinese hamster ovary (CHO-k1) cells. A cluster analysis was used to categorize these PFRs into three groups according to their structural characteristics and results from the HCS assay. Two groups, containing long-chain alkyl-PFRs and all aryl-PFRs, were found to cause mitochondrial impairment but showed different mechanisms of toxicity. Due to the high correlation between cell death and mitochondrial impairment, two PFRs with different structures, trihexyl phosphate (THP) and cresyl diphenyl phosphate (CDP), were selected and compared with chlorpyrifos (CPF) to elucidate their mechanism of inducing cell death. THP (an alkyl-PFR) was found to utilize a similar pathway as CPF to induce apoptosis. However, cell death induced by CDP (an aryl-PFR) was different from classical necrosis based on experiments to discriminate among the different modes of cell death. These results confirm that mitochondria might be important targets for some PFRs and that differently structured PFRs could function via distinct mechanisms of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of caspases prevents ototoxic and ongoing hair cell death

NASA Technical Reports Server (NTRS)

Matsui, Jonathan I.; Ogilvie, Judith M.; Warchol, Mark E.

2002-01-01

Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.

Automatic coding and selection of causes of death: an adaptation of Iris software for using in Brazil.

PubMed

Martins, Renata Cristófani; Buchalla, Cassia Maria

2015-01-01

To prepare a dictionary in Portuguese for using in Iris and to evaluate its completeness for coding causes of death. Iniatially, a dictionary with all illness and injuries was created based on the International Classification of Diseases - tenth revision (ICD-10) codes. This dictionary was based on two sources: the electronic file of ICD-10 volume 1 and the data from Thesaurus of the International Classification of Primary Care (ICPC-2). Then, a death certificate sample from the Program of Improvement of Mortality Information in São Paulo (PRO-AIM) was coded manually and by Iris version V4.0.34, and the causes of death were compared. Whenever Iris was not able to code the causes of death, adjustments were made in the dictionary. Iris was able to code all causes of death in 94.4% death certificates, but only 50.6% were directly coded, without adjustments. Among death certificates that the software was unable to fully code, 89.2% had a diagnosis of external causes (chapter XX of ICD-10). This group of causes of death showed less agreement when comparing the coding by Iris to the manual one. The software performed well, but it needs adjustments and improvement in its dictionary. In the upcoming versions of the software, its developers are trying to solve the external causes of death problem.

Found in Translation: How Preclinical Research Is Guiding the Clinical Development of the BCL2-Selective Inhibitor Venetoclax.

PubMed

Leverson, Joel D; Sampath, Deepak; Souers, Andrew J; Rosenberg, Saul H; Fairbrother, Wayne J; Amiot, Martine; Konopleva, Marina; Letai, Anthony

2017-12-01

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax. Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376-93. ©2017 AACR. ©2017 American Association for Cancer Research.

Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

PubMed

Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

2012-08-15

Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Fatal anaphylaxis registries data support changes in the who anaphylaxis mortality coding rules.

PubMed

Tanno, Luciana Kase; Simons, F Estelle R; Annesi-Maesano, Isabella; Calderon, Moises A; Aymé, Ségolène; Demoly, Pascal

2017-01-13

Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction. The difficulty of coding anaphylaxis fatalities under the World Health Organization (WHO) International Classification of Diseases (ICD) system is recognized as an important reason for under-notification of anaphylaxis deaths. On current death certificates, a limited number of ICD codes are valid as underlying causes of death, and death certificates do not include the word anaphylaxis per se. In this review, we provide evidences supporting the need for changes in WHO mortality coding rules and call for addition of anaphylaxis as an underlying cause of death on international death certificates. This publication will be included in support of a formal request to the WHO as a formal request for this move taking the 11 th ICD revision.

Evaluating the Use of an Electronic Death Registration System for Mortality Surveillance During and After Hurricane Sandy: New York City, 2012

PubMed Central

Li, Wenhui; Madsen, Ann M.; Wong, Howard; Das, Tara; Betancourt, Flor M.; Nicaj, Leze; Stayton, Catherine; Matte, Thomas; Begier, Elizabeth M.

2015-01-01

Objectives. We evaluated the use of New York City’s (NYC’s) electronic death registration system (EDRS) to conduct mortality surveillance during and after Hurricane Sandy. Methods. We used Centers for Disease Control and Prevention guidelines for surveillance system evaluation to gather evidence on usefulness, flexibility, stability, timeliness, and quality. We assessed system components, interviewed NYC Health Department staff, and analyzed 2010 to 2012 death records. Results. Despite widespread disruptions, NYC’s EDRS was stable and collected timely mortality data that were adapted to provide storm surveillance with minimal additional resources. Direct-injury fatalities and trends in excess all-cause mortality were rapidly identified, providing useful information for response; however, the time and burden of establishing reports, adapting the system, and identifying indirect deaths limited surveillance. Conclusions. The NYC Health Department successfully adapted its EDRS for near real-time disaster-related mortality surveillance. Retrospective assessment of deaths, advanced methods for case identification and analysis, standardized reports, and system enhancements will further improve surveillance. Local, state, and federal partners would benefit from partnering with vital records to develop EDRSs for surveillance and to promote ongoing evaluation. PMID:26378834

Cancer terminator viruses (CTV): A better solution for viral-based therapy of cancer.

PubMed

Emdad, Luni; Das, Swadesh K; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2018-08-01

In principle, viral gene therapy holds significant potential for the therapy of solid cancers. However, this promise has not been fully realized and systemic administration of viruses has not proven as successful as envisioned in the clinical arena. Our research is focused on developing the next generation of efficacious viruses to specifically treat both primary cancers and a major cause of cancer lethality, metastatic tumors (that have spread from a primary site of origin to other areas in the body and are responsible for an estimated 90% of cancer deaths). We have generated a chimeric tropism-modified type 5 and 3 adenovirus that selectively replicates in cancer cells and simultaneously produces a secreted anti-cancer toxic cytokine, melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24), referred to as a Cancer Terminator Virus (CTV) (Ad.5/3-CTV). In preclinical animal models, injection into a primary tumor causes selective cell death and therapeutic activity is also observed in non-injected distant tumors, that is, "bystander anti-tumor activity." To enhance the impact and therapeutic utility of the CTV, we have pioneered an elegant approach in which viruses are encapsulated in microbubbles allowing "stealth delivery" to tumor cells that when treated with focused ultrasound causes viral release killing tumor cells through viral replication, and producing and secreting MDA-7/IL-24, which stimulates the immune system to attack distant cancers, inhibits tumor angiogenesis and directly promotes apoptosis in distant cancer cells. This strategy is called UTMD (ultrasound-targeted microbubble-destruction). This novel CTV and UTMD approach hold significant promise for the effective therapy of primary and disseminated tumors. © 2017 Wiley Periodicals, Inc.

Resveratrol self-emulsifying system increases the uptake by endothelial cells and improves protection against oxidative stress-mediated death.

PubMed

Amri, Ahmed; Le Clanche, Solenn; Thérond, Patrice; Bonnefont-Rousselot, Dominique; Borderie, Didier; Lai-Kuen, René; Chaumeil, Jean-Claude; Sfar, Souad; Charrueau, Christine

2014-04-01

The aim of the present study was to develop and characterize a resveratrol self-emulsifying drug delivery system (Res-SEDDS), and to compare the uptake of resveratrol by bovine aortic endothelial cells (BAECs), and the protection of these cells against hydrogen peroxide-mediated cell death, versus a control resveratrol ethanolic solution. Three Res-SEDDSs were prepared and evaluated. The in vitro self-emulsification properties of these formulations, the droplet size and the zeta potential of the nanoemulsions formed on adding them to water under mild agitation conditions were studied, together with their toxicity on BAECs. An optimal atoxic formulation (20% Miglyol® 812, 70% Montanox® 80, 10% ethanol 96% v/v) was selected and further studied. Pre-incubation of BAECs for 180 min with 25 μM resveratrol in the nanoemulsion obtained from the selected SEDDS significantly increased the membrane and intracellular concentrations of resveratrol (for example, 0.076±0.015 vs. ethanolic solution 0.041±0.016 nmol/mg of protein after 60 min incubation, p<0.05). Resveratrol intracellular localization was confirmed by fluorescence confocal microscopy. Resveratrol nanoemulsion significantly improved the endothelial cell protection from H2O2-induced injury (750, 1000 and 1500 μM H2O2) in comparison with incubation with the control resveratrol ethanolic solution (for example, 55±6% vs. 38±5% viability after 1500 μM H2O2 challenge, p<0.05). In conclusion, formulation of resveratrol as a SEDDS significantly improved its cellular uptake and potentiated its antioxidant properties on BAECs. Copyright © 2013 Elsevier B.V. All rights reserved.

Adverse medical complications: an under-reported contributory cause of death in New York City.

PubMed

Gill, J R; Ely, S F; Toriello, A; Hirsch, C S

2014-04-01

The current death certification system in the USA fails to accurately track deaths due to adverse medical events. The aim of this study was to demonstrate the under-reporting of deaths due to adverse medical events due to limitations in the current death certification/reporting system, and the benefits of using the term 'therapeutic complication' as the manner of death. Retrospective review and comparison of death certificates and vital statistical coding. The manner of death is certified as a therapeutic complication when death is caused by predictable complications of appropriate therapy, and would not have occurred but for the medical intervention. Based on medical examiner records, complications that caused or contributed to deaths over a five-year period were examined retrospectively. These fatalities were compared with deaths coded as medical and surgical complications by the New York City Bureau of Vital Statistics. The Medical Examiner's Office certified 2471 deaths as therapeutic complications and 312 deaths as accidents occurring in healthcare facilities. In contrast, the New York City Bureau of Vital Statistics reported 188 deaths due to complications of medical and surgical care. Use of the term 'therapeutic complication' as the manner of death identified nearly 14 times more deaths than were reported by the New York City Bureau of Vital Statistics. If these therapeutic complications and medical accidents were considered as a 'disease', they would rank as the 10th leading cause of death in New York City, surpassing homicides and suicides in some years. Nationwide policy shifts that use the term 'therapeutic complication' would improve the capture and reporting of these deaths, thus allowing better identification of fatal adverse medical events in order to focus on and assess preventative strategies. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

A comparison of sisterhood information on causes of maternal death with the registration causes of maternal death in Matlab, Bangladesh.

PubMed

Shahidullah, M

1995-10-01

To explore whether causes of maternal death can be investigated using the sisterhood method, an indirect method for providing a community-based estimate of the level of maternal mortality, this study compares the sisterhood causes of maternal death with the Matlab Demographic Surveillance System's (DSS) causes of maternal death. Data for this study came from the Matlab DSS, which has been in operation since 1966 as a field site of the International Centre for Diarrhoeal Disease Research, Bangladesh. The maternal deaths that occurred during the 15-year period from 1976 to 1990 in the Matlab DSS area are the basis of this study. A sisterhood survey was conducted in Matlab in November and December 1991 to collect information on conditions, events and symptoms that preceded death. The collected information was evaluated to assign a most likely cause of maternal death. The sisterhood survey cause of maternal death was then compared with the DSS cause of maternal death. Cause of death could not be assigned with reasonable confidence for 34 (11%) of the 305 maternal deaths for which information was collected. For the remaining deaths, the agreement between the two classification systems was generally high for most cause-of-death categories considered. Though cause-of-death information obtained by the sisterhood method will always be subject to some error, it can provide an indication of an overall distribution of causes of maternal deaths. This data can be used for the planning of programmes aimed at reducing maternal mortality and for the evaluation of such programmes over time.

Estimating the burden of disease attributable to four selected environmental risk factors in South Africa.

PubMed

Norman, Rosana; Bradshaw, Debbie; Lewin, Simon; Cairncross, Eugene; Nannan, Nadine; Vos, Theo

2010-01-01

The first South African National Burden of Disease study quantified the underlying causes of premature mortality and morbidity experienced in South Africa in the year 2000. This was followed by a Comparative Risk Assessment to estimate the contributions of 17 selected risk factors to burden of disease in South Africa. This paper describes the health impact of exposure to four selected environmental risk factors: unsafe water, sanitation and hygiene; indoor air pollution from household use of solid fuels; urban outdoor air pollution and lead exposure. The study followed World Health Organization comparative risk assessment methodology. Population-attributable fractions were calculated and applied to revised burden of disease estimates (deaths and disability adjusted life years, [DALYs]) from the South African Burden of Disease study to obtain the attributable burden for each selected risk factor. The burden attributable to the joint effect of the four environmental risk factors was also estimated taking into account competing risks and common pathways. Monte Carlo simulation-modeling techniques were used to quantify sampling, uncertainty. Almost 24 000 deaths were attributable to the joint effect of these four environmental risk factors, accounting for 4.6% (95% uncertainty interval 3.8-5.3%) of all deaths in South Africa in 2000. Overall the burden due to these environmental risks was equivalent to 3.7% (95% uncertainty interval 3.4-4.0%) of the total disease burden for South Africa, with unsafe water sanitation and hygiene the main contributor to joint burden. The joint attributable burden was especially high in children under 5 years of age, accounting for 10.8% of total deaths in this age group and 9.7% of burden of disease. This study highlights the public health impact of exposure to environmental risks and the significant burden of preventable disease attributable to exposure to these four major environmental risk factors in South Africa. Evidence-based policies and programs must be developed and implemented to address these risk factors at individual, household, and community levels.

Seclusions and Restraints: Selected Cases of Death and Abuse at Public and Private Schools and Treatment Centers. Testimony Before the Committee on Education and Labor, House of Representatives. GAO-09-719T

ERIC Educational Resources Information Center

Kutz, Gregory D.

2009-01-01

The Government Accountability Office (GAO) recently testified before the Committee on Education and Labor, House of Representatives, regarding allegations of death and abuse at residential programs for troubled teens. The document presents the statement of Gregory D. Kutz, Managing Director, Forensic Audits and Special Investigations. Recent…

Long-term prognosis of patients with carbon monoxide poisoning: a nationwide cohort study.

PubMed

Huang, Chien-Cheng; Chung, Min-Hsien; Weng, Shih-Feng; Chien, Chih-Chiang; Lin, Shio-Jean; Lin, Hung-Jung; Guo, How-Ran; Su, Shih-Bin; Hsu, Chien-Chin; Juan, Chi-Wen

2014-01-01

Carbon monoxide poisoning (COP) often produces severe complications and can be fatal. Because this topic has not been well delineated, we investigated long-term prognoses of patients with COP (COP[+]). In this retrospective nationwide cohort study, 441 COP[+] patients and 8820 COP[-] controls (120) from 1999 to 2010 were selected from Taiwan's National Health Insurance Research Database. Thirty-seven (8.39%) COP[+] patients and 142 (1.61%) controls died (P<0.0001) during follow-up. Incidence rate ratios (IRR) of death were 5.24 times higher in COP[+] patients than in controls (P<0.0001). The risk of death was particularly high in the first month after COP (IRR: 308.78; 95% confidence interval [CI]: 40.79-2337.56), 1 to 6 months after (IRR: 18.92; 95% CI: 7.69-46.56), and 6-12 months after (IRR: 4.73; 95% CI: 1.02-21.90). After adjusting for age, gender, and selected comorbidities, the hazard ratio of death for COP[+] patients was still 4.097 times higher than for controls. Moreover, older age (≥30 years old), male gender, diabetes mellitus, hypertension, and low income were also independent mortality predictors. COP significantly increases the risk for long-term mortality. Early follow-up and secondary prevention of death are needed for patients with COP.

Fall Detection System for the Elderly Based on the Classification of Shimmer Sensor Prototype Data

PubMed Central

Ahmed, Moiz; Mehmood, Nadeem; Mehmood, Amir; Rizwan, Kashif

2017-01-01

Objectives Falling in the elderly is considered a major cause of death. In recent years, ambient and wireless sensor platforms have been extensively used in developed countries for the detection of falls in the elderly. However, we believe extra efforts are required to address this issue in developing countries, such as Pakistan, where most deaths due to falls are not even reported. Considering this, in this paper, we propose a fall detection system prototype that s based on the classification on real time shimmer sensor data. Methods We first developed a data set, ‘SMotion’ of certain postures that could lead to falls in the elderly by using a body area network of Shimmer sensors and categorized the items in this data set into age and weight groups. We developed a feature selection and classification system using three classifiers, namely, support vector machine (SVM), K-nearest neighbor (KNN), and neural network (NN). Finally, a prototype was fabricated to generate alerts to caregivers, health experts, or emergency services in case of fall. Results To evaluate the proposed system, SVM, KNN, and NN were used. The results of this study identified KNN as the most accurate classifier with maximum accuracy of 96% for age groups and 93% for weight groups. Conclusions In this paper, a classification-based fall detection system is proposed. For this purpose, the SMotion data set was developed and categorized into two groups (age and weight groups). The proposed fall detection system for the elderly is implemented through a body area sensor network using third-generation sensors. The evaluation results demonstrate the reasonable performance of the proposed fall detection prototype system in the tested scenarios. PMID:28875049

Investigation of unexplained infant deaths in Jerusalem, Israel 1996–2003

PubMed Central

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-01-01

Background Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. Methods We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996–2003. Results Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. Conclusions : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem. PMID:17074788

Meeting the Healthy People 2020 Objectives to Reduce Cancer Mortality.

PubMed

Weir, Hannah K; Thompson, Trevor D; Soman, Ashwini; Møller, Bjorn; Leadbetter, Steven; White, Mary C

2015-07-02

Healthy People 2020 (HP2020) calls for a 10% to 15% reduction in death rates from 2007 to 2020 for selected cancers. Trends in death rates can be used to predict progress toward meeting HP2020 targets. We used mortality data from 1975 through 2009 and population estimates and projections to predict deaths for all cancers and the top 23 cancers among men and women by race. We apportioned changes in deaths from population risk and population growth and aging. From 1975 to 2009, the number of cancer deaths increased among white and black Americans primarily because of an aging white population and a growing black population. Overall, age-standardized cancer death rates (risk) declined in all groups. From 2007 to 2020, rates are predicted to continue to decrease while counts of deaths are predicted to increase among men (15%) and stabilize among women (increase <10%). Declining death rates are predicted to meet HP2020 targets for cancers of the female breast, lung and bronchus, cervix and uterus, colon and rectum, oral cavity and pharynx, and prostate, but not for melanoma. Cancer deaths among women overall are predicted to increase by less than 10%, because of, in part, declines in breast, cervical, and colorectal cancer deaths among white women. Increased efforts to promote cancer prevention and improve survival are needed to counter the impact of a growing and aging population on the cancer burden and to meet melanoma target death rates.

Meeting the Healthy People 2020 Objectives to Reduce Cancer Mortality

PubMed Central

Thompson, Trevor D.; Soman, Ashwini; Møller, Bjorn; Leadbetter, Steven; White, Mary C.

2015-01-01

Introduction Healthy People 2020 (HP2020) calls for a 10% to 15% reduction in death rates from 2007 to 2020 for selected cancers. Trends in death rates can be used to predict progress toward meeting HP2020 targets. Methods We used mortality data from 1975 through 2009 and population estimates and projections to predict deaths for all cancers and the top 23 cancers among men and women by race. We apportioned changes in deaths from population risk and population growth and aging. Results From 1975 to 2009, the number of cancer deaths increased among white and black Americans primarily because of an aging white population and a growing black population. Overall, age-standardized cancer death rates (risk) declined in all groups. From 2007 to 2020, rates are predicted to continue to decrease while counts of deaths are predicted to increase among men (15%) and stabilize among women (increase <10%). Declining death rates are predicted to meet HP2020 targets for cancers of the female breast, lung and bronchus, cervix and uterus, colon and rectum, oral cavity and pharynx, and prostate, but not for melanoma. Conclusion Cancer deaths among women overall are predicted to increase by less than 10%, because of, in part, declines in breast, cervical, and colorectal cancer deaths among white women. Increased efforts to promote cancer prevention and improve survival are needed to counter the impact of a growing and aging population on the cancer burden and to meet melanoma target death rates. PMID:26133647

Ending of preventable deaths from pneumonia and diarrhoea: an achievable goal.

PubMed

Chopra, Mickey; Mason, Elizabeth; Borrazzo, John; Campbell, Harry; Rudan, Igor; Liu, Li; Black, Robert E; Bhutta, Zulfiqar A

2013-04-27

Global under-5 mortality has fallen rapidly from 12 million deaths in 1990, to 6·9 million in 2011; however, this number still falls short of the target of a two-thirds reduction or a maximum of 4 million deaths by 2015. Acceleration of reductions in deaths due to pneumonia and diarrhoea, which together account for about 2 million child deaths every year, is essential if the target is to be met. Scaling up of existing interventions against the two diseases to 80% and immunisation to 90% would eliminate more than two-thirds of deaths from these two diseases at a cost of US$6·715 billion by 2025. Modelling in this report shows that if all countries could attain the rates of decline of the regional leaders, then cause-specific death rates of fewer than three deaths per 1000 livebirths from pneumonia and less than one death per 1000 livebirths from diarrhoea could be achieved by 2025. These rates are those at which preventable deaths have been avoided. Increasing of awareness of the size of the problem; strengthening of leadership, intersectoral collaboration, and resource mobilisation; and increasing of efficiency through the selection of the optimum mix of a growing set of cost-effective interventions depending on local contexts are the priority actions needed to achieve the goal of ending preventable deaths from pneumonia and diarrhoea by 2025. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigation of unexplained infant deaths in Jerusalem, Israel 1996-2003.

PubMed

Eisenstein, Eli M; Haklai, Ziona; Schwartz, Shepard; Klar, Aharon; Stein, Nechama; Kerem, Eitan

2007-08-01

Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996-2003. Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem.

Does marital status predict the odds of suicidal death in taiwan? A seven-year population-based study.

PubMed

Yeh, Jui-Yuan; Xirasagar, Sudha; Liu, Tsai-Ching; Li, Chong-Yi; Lin, Herng-Ching

2008-06-01

Using nationwide, 7-year population-based data for 1997-2003, we examined marital status to see if it predicted suicide among the ethnic Chinese population of Taiwan. Using cause of death data, with a case-control design, two groups-total adult suicide deaths, n = 17,850, the study group, and adult deaths other than suicide, n = 71,400 (randomly selected from age, sex, and geographic region matched controls, four per suicide)-were studied. Using multiple logistic regression analysis including age-marital status interaction, adjusted estimates show divorced status to be the most detrimental for suicide propensity, with males showing stronger effect size. Females never married, aged below 35 and 65-plus, and widowed 65-plus had lower suicide odds.

Late Quaternary faulting along the Death Valley-Furnace Creek fault system, California and Nevada

USGS Publications Warehouse

Brogan, George E.; Kellogg, Karl; Slemmons, D. Burton; Terhune, Christina L.

1991-01-01

The Death Valley-Furnace Creek fault system, in California and Nevada, has a variety of impressive late Quaternary neotectonic features that record a long history of recurrent earthquake-induced faulting. Although no neotectonic features of unequivocal historical age are known, paleoseismic features from multiple late Quaternary events of surface faulting are well developed throughout the length of the system. Comparison of scarp heights to amount of horizontal offset of stream channels and the relationships of both scarps and channels to the ages of different geomorphic surfaces demonstrate that Quaternary faulting along the northwest-trending Furnace Creek fault zone is predominantly right lateral, whereas that along the north-trending Death Valley fault zone is predominantly normal. These observations are compatible with tectonic models of Death Valley as a northwest-trending pull-apart basin. The largest late Quaternary scarps along the Furnace Creek fault zone, with vertical separation of late Pleistocene surfaces of as much as 64 m (meters), are in Fish Lake Valley. Despite the predominance of normal faulting along the Death Valley fault zone, vertical offset of late Pleistocene surfaces along the Death Valley fault zone apparently does not exceed about 15 m. Evidence for four to six separate late Holocene faulting events along the Furnace Creek fault zone and three or more late Holocene events along the Death Valley fault zone are indicated by rupturing of Q1B (about 200-2,000 years old) geomorphic surfaces. Probably the youngest neotectonic feature observed along the Death Valley-Furnace Creek fault system, possibly historic in age, is vegetation lineaments in southernmost Fish Lake Valley. Near-historic faulting in Death Valley, within several kilometers south of Furnace Creek Ranch, is represented by (1) a 2,000-year-old lake shoreline that is cut by sinuous scarps, and (2) a system of young scarps with free-faceted faces (representing several faulting events) that cuts Q1B surfaces.

Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

PubMed Central

Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

2014-01-01

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

An assessment of non-communicable diseases, diabetes, and related risk factors in the Republic of the Marshall Islands, Majuro Atoll: a systems perspective.

PubMed

Ichiho, Henry M; deBrum, Ione; Kedi, Shra; Langidrik, Justina; Aitaoto, Nia

2013-05-01

Non-communicable diseases (NCD) have been identified as a health emergency in the US-associated Pacific Islands (USAPI).1 This assessment, funded by the National Institutes of Health, was conducted in the Republic of the Marshall Islands, Majuro Atoll and describes the burdens due to selected NCD (diabetes, heart disease, hypertension, stroke, chronic kidney disease); and assesses the system of service capacity and current activities for service delivery, data collection and reporting as well as identifying the issues that need to be addressed. Findings reveal that the risk factors of poor diet, lack of physical activity, and risky lifestyle behaviors are associated with overweight and obesity and subsequent NCD that are significant factors in the morbidity and mortality of the population. The leading causes of death include sepsis, cancer, diabetes-related deaths, pneumonia, and hypertension. Population-based survey for the RMI show that 62.5% of the adults are overweight or obese and the prevalence of diabetes stands at 19.6%. Other findings show significant gaps in the system of administrative, clinical, data, and support services to address these NCD. There is no policy and procedure manual for the hospital or public health diabetes clinics and there is little communication, coordination, or collaboration between the medical and public health staff. There is no functional data system that allows for the identification, registry, or tracking of patients with diabetes or other NCDs. Based on these findings, priority issues and problems to be addressed for the administrative, clinical, and data systems were identified.

An Assessment of Non-Communicable Diseases, Diabetes, and Related Risk Factors in the Republic of the Marshall Islands, Majuro Atoll: A Systems Perspective

PubMed Central

deBrum, Ione; Kedi, Shra; Langidrik, Justina; Aitaoto, Nia

2013-01-01

Non-communicable diseases (NCD) have been identified as a health emergency in the US-associated Pacific Islands (USAPI).1 This assessment, funded by the National Institutes of Health, was conducted in the Republic of the Marshall Islands, Majuro Atoll and describes the burdens due to selected NCD (diabetes, heart disease, hypertension, stroke, chronic kidney disease); and assesses the system of service capacity and current activities for service delivery, data collection and reporting as well as identifying the issues that need to be addressed. Findings reveal that the risk factors of poor diet, lack of physical activity, and risky lifestyle behaviors are associated with overweight and obesity and subsequent NCD that are significant factors in the morbidity and mortality of the population. The leading causes of death include sepsis, cancer, diabetes-related deaths, pneumonia, and hypertension. Population-based survey for the RMI show that 62.5% of the adults are overweight or obese and the prevalence of diabetes stands at 19.6%. Other findings show significant gaps in the system of administrative, clinical, data, and support services to address these NCD. There is no policy and procedure manual for the hospital or public health diabetes clinics and there is little communication, coordination, or collaboration between the medical and public health staff. There is no functional data system that allows for the identification, registry, or tracking of patients with diabetes or other NCDs. Based on these findings, priority issues and problems to be addressed for the administrative, clinical, and data systems were identified. PMID:23901367

An emergentist vs a linear approach to social change processes: a gender look in contemporary India between modernity and Hindu tradition.

PubMed

Condorelli, Rosalia

2015-01-01

Using Census of India data from 1901 to 2011 and national and international reports on women's condition in India, beginning with sex ratio trends according to regional distribution up to female infanticides and sex-selective abortions and dowry deaths, this study examines the sociological aspects of the gender imbalance in modern contemporary India. Gender inequality persistence in India proves that new values and structures do not necessarily lead to the disappearance of older forms, but they can co-exist with mutual adaptations and reinforcements. Data analysis suggests that these unexpected combinations are not comprehensible in light of a linear concept of social change which is founded, in turn, on a concept of social systems as linear interaction systems that relate to environmental perturbations according to proportional cause and effect relationships. From this perspective, in fact, behavioral attitudes and interaction relationships should be less and less proportionally regulated by traditional values and practices as exposure to modernizing influences increases. And progressive decreases should be found in rates of social indicators of gender inequality like dowry deaths (the inverse should be found in sex ratio trends). However, data does not confirm these trends. This finding leads to emphasize a new theoretical and methodological approach toward social systems study, namely the conception of social systems as complex adaptive systems and the consequential emergentist, nonlinear conception of social change processes. Within the framework of emergentist theory of social change is it possible to understand the lasting strength of the patriarchal tradition and its problematic consequences in the modern contemporary India.

Surveillance for Violent Deaths -
National Violent Death Reporting System, 18 States, 2014.

PubMed

Fowler, Katherine A; Jack, Shane P D; Lyons, Bridget H; Betz, Carter J; Petrosky, Emiko

2018-02-02

In 2014, approximately 59,000 persons died in the United States as a result of violence-related injuries. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) regarding violent deaths from 18 U.S. states for 2014. Results are reported by sex, age group, race/ethnicity, marital status, location of injury, method of injury, circumstances of injury, and other selected characteristics. 2014. NVDRS collects data from participating states regarding violent deaths. Data are obtained from death certificates, coroner/medical examiner reports, law enforcement reports, and secondary sources (e.g., child fatality review team data, supplemental homicide reports, hospital data, and crime laboratory data). This report includes data from 18 states that collected statewide data for 2014 (Alaska, Colorado, Georgia, Kentucky, Maryland, Massachusetts, Michigan, New Jersey, New Mexico, North Carolina, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Virginia, and Wisconsin). NVDRS collates documents for each death and links deaths that are related (e.g., multiple homicides, a homicide followed by a suicide, or multiple suicides) into a single incident. For 2014, a total of 22,098 fatal incidents involving 22,618 deaths were captured by NVDRS in the 18 states included in this report. The majority of deaths were suicides (65.6%), followed by homicides (22.5%), deaths of undetermined intent (10.0%), deaths involving legal intervention (1.3%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force, excluding legal executions), and unintentional firearm deaths (<1%). The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision (ICD-10) and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement. Suicides occurred at higher rates among males, non-Hispanic American Indian/Alaska Natives (AI/AN), non-Hispanic whites, persons aged 45-54 years, and males aged ≥75 years. Suicides were preceded primarily by a mental health, intimate partner, substance abuse, or physical health problem or a crisis during the previous or upcoming 2 weeks. Homicide rates were higher among males and persons aged <1 year and 15-44 years; rates were highest among non-Hispanic black and AI/AN males. Homicides primarily were precipitated by arguments and interpersonal conflicts, occurrence in conjunction with another crime, or related to intimate partner violence (particularly for females). When the relationship between a homicide victim and a suspected perpetrator was known, it was most often either an acquaintance/friend or an intimate partner. Legal intervention death rates were highest among males and persons aged 20-44 years; rates were highest among non-Hispanic black males and Hispanic males. Precipitating factors for the majority of legal intervention deaths were alleged criminal activity in progress, the victim reportedly using a weapon in the incident, a mental health or substance abuse problem, an argument or conflict, or a recent crisis. Deaths of undetermined intent occurred more frequently among males, particularly non-Hispanic black and AI/AN males, and persons aged 30-54 years. Substance abuse, mental health problems, physical health problems, and a recent crisis were the most common circumstances preceding deaths of undetermined intent. Unintentional firearm deaths were more frequent among males, non-Hispanic whites, and persons aged 10-24 years; these deaths most often occurred while the shooter was playing with a firearm and were most often precipitated by a person unintentionally pulling the trigger or mistakenly thinking the firearm was unloaded. This report provides a detailed summary of data from NVDRS for 2014. The results indicate that violent deaths resulting from self-inflicted or interpersonal violence disproportionately affected persons aged <65 years, males, and certain minority populations. The primary precipitating factors for homicides and suicides were intimate partner problems, interpersonal conflicts, mental health and substance abuse problems, and recent crises. NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in the development, implementation, and evaluation of programs and policies to reduce and prevent violent deaths. For example, North Carolina VDRS data were used to improve case ascertainment of pregnancy-associated suicides, Wisconsin VDRS data were used to develop the statewide suicide prevention strategy, and Colorado VDRS data were used to develop programs and prevention strategies for suicide among veterans. The continued development and expansion of NVDRS to include all U.S. states, territories, and the District of Columbia are essential to public health efforts to reduce the impact of violence.

Work-related fatalities among youth ages 11-17 in North Carolina, 1990-2008.

PubMed

Rauscher, Kimberly J; Runyan, Carol W; Radisch, Deborah

2011-02-01

Local and national surveillance systems are in place that identify occupational deaths. However, due to certain restrictions, they are limited in their ability to accurately count these deaths among adolescent workers. In this population-based study, we relied on primary data from the North Carolina medical examiner system to identify and describe all work-related fatalities among North Carolina youth under age 18 between 1990 and 2008. We identified 31 work-related deaths among youth ages 11-17. The majority occurred between 1990 and 1999. Most occurred in construction and agriculture. Vehicles and guns were responsible for the majority of deaths. Although the prevalence of adolescent work-related fatalities has seen a decline in North Carolina, the 31 deaths we detected signal a failure of the systems in place to prevent young worker fatalities. More remains to be done to protect the lives of adolescent workers. Copyright © 2010 Wiley-Liss, Inc.

Compartmentalized oxidative stress in dopaminergic cell death induced by pesticides and complex I inhibitors: Distinct roles of superoxide anion and superoxide dismutases

PubMed Central

Rodriguez-Rocha, Humberto; Garcia-Garcia, Aracely; Pickett, Chillian; Sumin, Li; Jones, Jocelyn; Chen, Han; Webb, Brian; Choi, Jae; Zhou, You; Zimmerman, Matthew C.; Franco, Rodrigo

2013-01-01

The loss of dopaminergic neurons induced by the parkinsonian toxins paraquat, rotenone and 1-methyl-4-phenylpyridinium (MPP+) is associated with oxidative stress. However, controversial reports exist regarding the source/compartmentalization of reactive oxygen species (ROS) generation and its exact role in cell death. We aimed to determine in detail the role of superoxide anion (O2•−), oxidative stress and their subcellular compartmentalization in dopaminergic cell death induced by parkinsonian toxins. Oxidative stress and ROS formation was determined in the cytosol, intermembrane (IMS) and mitochondrial matrix compartments, using dihydroethidine derivatives, the redox sensor roGFP, as well as electron paramagnetic resonance spectroscopy. Paraquat induced an increase in ROS and oxidative stress in both the cytosol and mitochondrial matrix prior to cell death. MPP+ and rotenone primarily induced an increase in ROS and oxidative stress in the mitochondrial matrix. No oxidative stress was detected at the level of the IMS. In contrast to previous studies, overexpression of manganese superoxide dismutase (MnSOD) or copper/zinc SOD (CuZnSOD) had no effect on ROS steady state levels, lipid peroxidation, loss of mitochondrial membrane potential (ΔΨm) and dopaminergic cell death induced by MPP+ or rotenone. In contrast, paraquat-induced oxidative stress and cell death were selectively reduced by MnSOD overexpression, but not by CuZnSOD or manganese-porphyrins. However, MnSOD also failed to prevent ΔΨm loss. Finally, paraquat, but not MPP+ or rotenone, induced the transcriptional activation the redox-sensitive antioxidant response elements (ARE) and nuclear factor kappa-B (NF-κB). These results demonstrate a selective role of mitochondrial O2•− in dopaminergic cell death induced by paraquat, and show that toxicity induced by the complex I inhibitors rotenone and MPP+ does not depend directly on mitochondrial O2•− formation. PMID:23602909

Cardiopulmonary Arrest and Resuscitation Disrupts Cholinergic Anti-Inflammatory Processes: A Role for Cholinergic α7 Nicotinic Receptors

PubMed Central

Morris, John S.; Karelina, Kate; Weil, Zachary M.; Zhang, Ning; Al-Abed, Yousef; Brothers, Holly M.; Wenk, Gary L.; Pavlov, Valentin A.; Tracey, Kevin J.; DeVries, A. Courtney

2011-01-01

Cardiac arrest is a leading cause of death worldwide. While survival rates following sudden cardiac arrest remain relatively low, recent advancements in patient care have begun to increase the proportion of individuals who survive cardiac arrest. However, many of these individuals subsequently develop physiological and psychiatric conditions that likely result from ongoing neuroinflammation and neuronal death. The present study was conducted to better understand the pathophysiological effects of cardiac arrest on neuronal cell death and inflammation, and their modulation by the cholinergic system. Using a well validated model of cardiac arrest, here we show that global cerebral ischemia increases microglial activation, proinflammatory cytokine mRNA expression (interleukin-1β, interleukin-6, tumor necrosis factor-α), and neuronal damage. Cardiac arrest also induces alterations in numerous cellular components of central cholinergic signaling, including a reduction in choline acetyltransferase enzymatic activity and the number of choline acetyltransferase-positive neurons, as well as, reduced acetylcholinesterase and vesicular acetylcholine transporter mRNA. However, treatment with a selective agonist of the α7 nicotinic acetylcholine receptor, the primary receptor mediating the cholinergic anti-inflammatory pathway, significantly decreases the neuroinflammation and neuronal damage resulting from cardiac arrest. These data suggest that global cerebral ischemia results in significant declines in central cholinergic signaling, which may in turn diminish the capacity of the cholinergic anti-inflammatory pathway to control inflammation. Furthermore, we provide evidence that pharmacological activation of α7 nicotinic acetylcholine receptors provide significant protection against ischemia-related cell death and inflammation within a clinically relevant time frame. PMID:21368056

Relationship of opioid prescription sales and overdoses, North Carolina.

PubMed

Modarai, F; Mack, K; Hicks, P; Benoit, S; Park, S; Jones, C; Proescholdbell, S; Ising, A; Paulozzi, L

2013-09-01

In the United States, fatal drug overdoses have tripled since 1991. This escalation in deaths is believed to be driven primarily by prescription opioid medications. This investigation compared trends and patterns in sales of opioids, opioid drug overdoses treated in emergency departments (EDs), and unintentional overdose deaths in North Carolina (NC). Our ecological study compared rates of opioid sales, opioid related ED overdoses, and unintentional drug overdose deaths in NC. Annual sales data, provided by the Drug Enforcement Administration, for select opioids were converted into morphine equivalents and aggregated by zip code. These opioid drug sales rates were trended from 1997 to 2010. In addition, opioid sales were correlated and compared to opioid related ED visits, which came from a Centers for Disease Control and Prevention syndromic surveillance system, and unintentional overdose deaths, which came from NC Vital Statistics, from 2008 to 2010. Finally, spatial cluster analysis was performed and rates were mapped by zip code in 2010. Opioid sales increased substantially from 1997 to 2010. From 2008 to 2010, the quarterly rates of opioid drug overdoses treated in EDs and opioid sales correlated (r=0.68, p=0.02). Specific regions of the state, particularly in the southern and western corners, had both high rates of prescription opioid sales and overdoses. Temporal trends in sales of prescription opioids correlate with trends in opioid related ED visits. The spatial correlation of opioid sales with ED visit rates shows that opioid sales data may be a timely way to identify high-risk communities in the absence of timely ED data. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Making COD statistics useful for public health at local level in the city of Cape Town: utilidad para la salud pública a nivel local en Ciudad del Cabo.

PubMed Central

Bradshaw, Debbie; Groenewald, Pamela; Bourne, David E.; Mahomed, Hassan; Nojilana, Beatrice; Daniels, Johan; Nixon, Jo

2006-01-01

OBJECTIVE: To review the quality of the coding of the cause of death (COD) statistics and assess the mortality information needs of the City of Cape Town. METHODS: Using an action research approach, a study was set up to investigate the quality of COD information, the accuracy of COD coding and consistency of coding practices in the larger health subdistricts. Mortality information needs and the best way of presenting the statistics to assist health managers were explored. FINDINGS: Useful information was contained in 75% of death certificates, but nearly 60% had only a single cause certified; 55% of forms were coded accurately. Disagreement was mainly because routine coders coded the immediate instead of the underlying COD. An abridged classification of COD, based on causes of public health importance, prevalent causes and selected combinations of diseases was implemented with training on underlying cause. Analysis of the 2001 data identified the leading causes of death and premature mortality and illustrated striking differences in the disease burden and profile between health subdistricts. CONCLUSION: Action research is particularly useful for improving information systems and revealed the need to standardize the coding practice to identify underlying cause. The specificity of the full ICD classification is beyond the level of detail on the death certificates currently available. An abridged classification for coding provides a practical tool appropriate for local level public health surveillance. Attention to the presentation of COD statistics is important to enable the data to inform decision-makers. PMID:16583080

Making COD statistics useful for public health at local level in the city of Cape Town: utilidad para la salud pública a nivel local en Ciudad del Cabo.

PubMed

Bradshaw, Debbie; Groenewald, Pamela; Bourne, David E; Mahomed, Hassan; Nojilana, Beatrice; Daniels, Johan; Nixon, Jo

2006-03-01

To review the quality of the coding of the cause of death (COD) statistics and assess the mortality information needs of the City of Cape Town. Using an action research approach, a study was set up to investigate the quality of COD information, the accuracy of COD coding and consistency of coding practices in the larger health subdistricts. Mortality information needs and the best way of presenting the statistics to assist health managers were explored. Useful information was contained in 75% of death certificates, but nearly 60% had only a single cause certified; 55% of forms were coded accurately. Disagreement was mainly because routine coders coded the immediate instead of the underlying COD. An abridged classification of COD, based on causes of public health importance, prevalent causes and selected combinations of diseases was implemented with training on underlying cause. Analysis of the 2001 data identified the leading causes of death and premature mortality and illustrated striking differences in the disease burden and profile between health subdistricts. Action research is particularly useful for improving information systems and revealed the need to standardize the coding practice to identify underlying cause. The specificity of the full ICD classification is beyond the level of detail on the death certificates currently available. An abridged classification for coding provides a practical tool appropriate for local level public health surveillance. Attention to the presentation of COD statistics is important to enable the data to inform decision-makers.

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

PubMed

Orban, Jean-Christophe; Walrave, Yannick; Mongardon, Nicolas; Allaouchiche, Bernard; Argaud, Laurent; Aubrun, Frédéric; Barjon, Geneviève; Constantin, Jean-Michel; Dhonneur, Gilles; Durand-Gasselin, Jacques; Dupont, Hervé; Genestal, Michèle; Goguey, Chloé; Goutorbe, Philippe; Guidet, Bertrand; Hyvernat, Hervé; Jaber, Samir; Lefrant, Jean-Yves; Mallédant, Yannick; Morel, Jerôme; Ouattara, Alexandre; Pichon, Nicolas; Guérin Robardey, Anne-Marie; Sirodot, Michel; Theissen, Alexandre; Wiramus, Sandrine; Zieleskiewicz, Laurent; Leone, Marc; Ichai, Carole

2017-05-01

Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts. An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest). A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths. In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Selective eradication of cancer cells by delivery of adenovirus-based toxins

PubMed Central

Shapira, Shiran; Shapira, Assaf; Kazanov, Diana; Hevroni, Gil; Kraus, Sarah; Arber, Nadir

2017-01-01

Background and objective KRAS mutation is an early event in colorectal cancer carcinogenesis. We previously reported that a recombinant adenovirus, carrying a pro-apoptotic gene (PUMA) under the regulation of Ets/AP1 (RAS-responsive elements) suppressed the growth of cancer cells harboring hyperactive KRAS. We propose to exploit the hyperactive RAS pathway, rather than to inhibit it as was previously tried and failed repeatedly. We aim to improve efficacy by substituting PUMA with a more potent toxin, the bacterial MazF-MazE toxin-antitoxin system, under a very tight regulation. Results A massive cell death, in a dose-dependent manner, reaching 73% at MOI 10 was seen in KRAS cells as compared to 22% in WT cells. Increase expression of MazE (the anti-toxin) protected normal cells from any possible internal or external leakage of the system and confirmed the selectivity, specificity and safety of the targeting system. Considerable tumor shrinkage (61%) was demonstrated in vivo following MazEF-encoding adenovirus treatment without any side effects. Design Efficient vectors for cancer-directed gene delivery were constructed; “pAdEasy-Py4-SV40mP-mCherry-MazF”“pAdEasy-Py4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES-EGFP“,“pAdEasy-ΔPy4-SV40mP-mCherry-MazF-IRES-TetR-CMVmp-MazE-IRES-EGFP “and “pAdEasy-mCherry”. Virus particles were produced and their potency was tested. Cell death was measured qualitatively by using the fluorescent microscopy and colony formation assay, and was quantified by MTT. FACS analysis using annexin V and RedDot2 dyes was performed for measuring apoptotic and dead cells, respectively. In vivo tumor formation was measured in a xenograft model. Conclusions A proof of concept for a novel cancer safe and effective gene therapy exploiting an aberrant hyperactive pathway is achievable. PMID:28445136

36 CFR 7.26 - Death Valley National Monument.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Death Valley National... INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.26 Death Valley National Monument. (a) Mining. Mining in Death Valley National Monument is subject to the following regulations, which are...

5 CFR 843.302 - Time for filing applications for death benefits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Time for filing applications for death... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.302 Time for filing applications for death benefits. A current or...

5 CFR 843.309 - Basic employee death benefit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Basic employee death benefit. 843.309... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.309 Basic employee death benefit. (a) Except as provided in § 843.312, if an...

5 CFR 843.308 - Supplementary benefits on death of a retiree.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Supplementary benefits on death of a... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.308 Supplementary benefits on death of a retiree. (a) Except as...

5 CFR 843.309 - Basic employee death benefit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Basic employee death benefit. 843.309... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.309 Basic employee death benefit. (a) Except as provided in § 843.312, if an...

5 CFR 843.309 - Basic employee death benefit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Basic employee death benefit. 843.309... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.309 Basic employee death benefit. (a) Except as provided in § 843.312, if an...

5 CFR 843.309 - Basic employee death benefit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Basic employee death benefit. 843.309... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.309 Basic employee death benefit. (a) Except as provided in § 843.312, if an...

5 CFR 843.309 - Basic employee death benefit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Basic employee death benefit. 843.309... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.309 Basic employee death benefit. (a) Except as provided in § 843.312, if an...

5 CFR 843.302 - Time for filing applications for death benefits.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Time for filing applications for death... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.302 Time for filing applications for death benefits. A current or...

5 CFR 843.308 - Supplementary benefits on death of a retiree.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Supplementary benefits on death of a... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.308 Supplementary benefits on death of a retiree. (a) Except as...

5 CFR 843.308 - Supplementary benefits on death of a retiree.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Supplementary benefits on death of a... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.308 Supplementary benefits on death of a retiree. (a) Except as...

5 CFR 843.302 - Time for filing applications for death benefits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Time for filing applications for death... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.302 Time for filing applications for death benefits. A current or...

5 CFR 843.302 - Time for filing applications for death benefits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Time for filing applications for death... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.302 Time for filing applications for death benefits. A current or...

Violent Deaths Among Georgia Workers: An Examination of Suicides and Homicides by Occupation, 2006-2009.

PubMed

Lavender, Antionette; Ramirez-Irizarry, Viani; Bayakly, A Rana; Koplan, Carol; Bryan, J Michael

2016-11-01

Workers in certain occupations may be at an increased risk of a violent-related death such as homicide or suicide. The purpose of this study is to describe rates of violent deaths among Georgia workers by occupation, including cases occurring at work and outside of the workplace, and identify leading circumstances surrounding suicides and homicides for the occupations most at risk. Data from the 2006-2009 Georgia Violent Death Reporting System were used. Occupational text fields were recoded into 23 major occupation categories based on the 2010 Standard Occupational Classification system. Crude rates and standardized mortality ratios for violent deaths (suicides and homicides) were calculated by occupation among Georgia workers aged ≥16 years. The leading circumstances precipitating violent deaths among the high-risk occupations were described. Analyses were conducted during 2012-2013 and 2015. A total of 4,616 Georgia resident workers were victims of a violent death during 2006-2009. Of these deaths, 2,888 (62.6%) were suicides and 1,728 (37.4%) were homicides. Farming, fishing, and forestry occupations had the highest rate of violent deaths at 80.5 per 100,000 workers followed by construction and extraction occupations at 65.5 per 100,000. The most common suicide circumstances among workers were having a current depressed mood, a current mental health problem, and an intimate partner problem. Use of the Violent Death Reporting System provides a unique opportunity to explore violent deaths among workers. This analysis shows the need to ensure that workers have access to workplace and community-based suicide and violence prevention services. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Number of Heat Wave Deaths by Diagnosis, Sex, Age Groups, and Area, in Slovenia, 2015 vs. 2003

PubMed Central

Perčič, Simona; Kukec, Andreja; Cegnar, Tanja; Hojs, Ana

2018-01-01

Background: Number of deaths increases during periods of elevated heat. Objectives: To examine whether differences in heat-related deaths between 2003 and 2015 occurred in Slovenia. Materials and Methods: We estimated relative risks for deaths for the observed diagnoses, sex, age, and area, as well as 95% confidence intervals and excess deaths associated with heat waves occurring in 2015 and 2003. For comparison between 2015 and 2003, we calculated relative risks ratio and 95% confidence intervals. Results: Statistically significant in 2015 were the following: age group 75+, all causes of deaths (RR = 1.10, 95% CI 1.00–1.22); all population, circulatory system diseases (RR = 1.14, 95% CI 1.01–1.30) and age group 75+, diseases of circulatory system (RR = 1.17, 95% CI 1.01–1.34). Statistically significant in 2003 were the following: female, age group 5–74, circulatory system diseases (RR = 1.69, 95% CI 1.08–2.62). Discussion: Comparison between 2015 and 2003, all, circulatory system diseases (RRR = 1.25, 95% CI 1.01–1.55); male, circulatory system diseases (RRR = 1.85, 95% CI 1.41–2.43); all, age group 75+ circulatory system diseases (RRR = 1.34, 95% CI 1.07–1.69); male, age group 75+, circulatory system diseases (RRR = 1.52, 95% CI 1.03–2.25) and female, age group 75+, circulatory system diseases (RRR = 1.43, 95% CI 1.08–1.89). Conclusions: Public health efforts are urgent and should address circulatory system causes and old age groups. PMID:29361792

Simple Scoring System to Predict In-Hospital Mortality After Surgery for Infective Endocarditis.

PubMed

Gatti, Giuseppe; Perrotti, Andrea; Obadia, Jean-François; Duval, Xavier; Iung, Bernard; Alla, François; Chirouze, Catherine; Selton-Suty, Christine; Hoen, Bruno; Sinagra, Gianfranco; Delahaye, François; Tattevin, Pierre; Le Moing, Vincent; Pappalardo, Aniello; Chocron, Sidney

2017-07-20

Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. Outcomes of 361 consecutive patients (mean age, 59.1±15.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m 2 (odds ratio [OR], 1.79; P =0.049), estimated glomerular filtration rate <50 mL/min (OR, 3.52; P <0.0001), New York Heart Association class IV (OR, 2.11; P =0.024), systolic pulmonary artery pressure >55 mm Hg (OR, 1.78; P =0.032), and critical state (OR, 2.37; P =0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Changing epidemiology of trauma deaths leads to a bimodal distribution

PubMed Central

Gunst, Mark; Ghaemmaghami, Vafa; Gruszecki, Amy; Urban, Jill; Frankel, Heidi

2010-01-01

Injury mortality was classically described with a trimodal distribution, with immediate deaths at the scene, early deaths due to hemorrhage, and late deaths from organ failure. We hypothesized that the development of trauma systems has improved prehospital care, early resuscitation, and critical care and altered this pattern. This population-based study of all trauma deaths in an urban county with a mature trauma system reviewed data for 678 patients (median age, 33 years; 81% male; 43% gunshot, 20% motor vehicle crashes). Deaths were classified as immediate (scene), early (in hospital, ≤4 hours from injury), or late (>4 hours after injury). Multinomial regression was used to identify independent predictors of immediate and early versus late deaths, adjusted for age, gender, race, intention, mechanism, toxicology, and cause of death. Results showed 416 (61%) immediate, 199 (29%) early, and 63 (10%) late deaths. Compared with the classical description, the percentage of immediate deaths remained unchanged, and early deaths occurred much earlier (median 52 vs 120 minutes). However, unlike the classic trimodal distribution, the late peak was greatly diminished. Intentional injuries, alcohol intoxication, asphyxia, and injuries to the head and chest were independent predictors of immediate death. Alcohol intoxication and injuries to the chest were predictors of early death, while pelvic fractures and blunt assaults were associated with late deaths. In conclusion, trauma deaths now have a predominantly bimodal distribution. Near elimination of the late peak likely represents advancements in resuscitation and critical care that have reduced organ failure. Further reductions in mortality will likely come from prevention of intentional injuries and injuries associated with alcohol intoxication. PMID:20944754

Accuracy of death certification of dementia in population-based samples of older people: analysis over time

PubMed Central

Calloway, Rowan; Zhao, Emily; Brayne, Carol

2018-01-01

Abstract Background death certification data are routinely collected in most developed countries. Coded causes of death are a readily accessible source and have the potential advantage of providing complete follow-up, but with limitations. Objective to investigate the reliability of using death certificates for surveillance of dementia, the time trend of recording dementia on death certificates and predictive factors of recording of dementia. Subjects individuals aged 65 and over in six areas across England and Wales were randomly selected for the Medical Research Council Cognitive Function and Ageing Study (CFAS) and CFAS II with mortality follow-up. Methods prevalence of dementia recorded on death certificates were calculated by year. Reporting of dementia on death certificates compared with the study diagnosis of dementia, with sensitivity, specificity and Cohen’s κ were estimated. Multivariable logistic regression models explored the impact of potential factors on the reporting of dementia on the death certificate. Results the overall unadjusted prevalence of dementia on death certificates rose from 5.3% to 25.9% over the last 26 years. Dementia reported on death certificates was poor with sensitivity 21.0% in earlier cohort CFAS, but it had increased to 45.2% in CFAS II. Dementia was more likely to be recorded on death certificates in individuals with severe dementia, or those living in an institution, yet less likely reported if individuals died in hospital. Conclusion recording dementia on death certificate has improved significantly in the England and Wales. However, such information is still an underestimate and should be used alongside epidemiological estimations. PMID:29718074

Protozoacidal Trojan-Horse: use of a ligand-lytic peptide for selective destruction of symbiotic protozoa within termite guts.

PubMed

Sethi, Amit; Delatte, Jennifer; Foil, Lane; Husseneder, Claudia

2014-01-01

For novel biotechnology-based termite control, we developed a cellulose bait containing freeze-dried genetically engineered yeast which expresses a protozoacidal lytic peptide attached to a protozoa-recognizing ligand. The yeast acts as a 'Trojan-Horse' that kills the cellulose-digesting protozoa in the termite gut, which leads to the death of termites, presumably due to inefficient cellulose digestion. The ligand targets the lytic peptide specifically to protozoa, thereby increasing its protozoacidal efficiency while protecting non-target organisms. After ingestion of the bait, the yeast propagates in the termite's gut and is spread throughout the termite colony via social interactions. This novel paratransgenesis-based strategy could be a good supplement for current termite control using fortified biological control agents in addition to chemical insecticides. Moreover, this ligand-lytic peptide system could be used for drug development to selectively target disease-causing protozoa in humans or other vertebrates.

Administration of the antitumor drug mitoguazone protects normal thymocytes against spontaneous and etoposide-induced apoptosis.

PubMed

Ferioli, M E; Bottone, M G; Soldani, C; Pellicciari, C

2004-11-01

The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.

Maternal mortality in Mexico, beyond millennial development objectives: An age-period-cohort model.

PubMed

Rodríguez-Aguilar, Román

2018-01-01

The maternal mortality situation is analyzed in México as an indicator that reflects the social development level of the country and was one of the millennial development objectives. The effect of a maternal death in the related social group has multiplier effects, since it involves family dislocation, economic impact and disruption of the orphans' normal social development. Two perspectives that causes of maternal mortality were analyzed, on one hand, their relationship with social determinants and on the other, factors directly related to the health system. Evidence shows that comparing populations based on group of selected variables according to social conditions and health care access, statistically significant differences prevail according to education and marginalization levels, and access to medical care. In addition, the Age-Period-Cohort model raised, shows significant progress in terms of a downward trend in maternal mortality in a generational level. Those women born before 1980 had a greater probability of maternal death in relation to recent generations, which is a reflection of the improvement in social determinants and in the Health System. The age effect shows a problem in maternal mortality in women under 15 years old, so teen pregnancy is a priority in health and must be addressed in short term. There is no clear evidence of a period effect.

Maternal mortality in Mexico, beyond millennial development objectives: An age-period-cohort model

PubMed Central

2018-01-01

The maternal mortality situation is analyzed in México as an indicator that reflects the social development level of the country and was one of the millennial development objectives. The effect of a maternal death in the related social group has multiplier effects, since it involves family dislocation, economic impact and disruption of the orphans' normal social development. Two perspectives that causes of maternal mortality were analyzed, on one hand, their relationship with social determinants and on the other, factors directly related to the health system. Evidence shows that comparing populations based on group of selected variables according to social conditions and health care access, statistically significant differences prevail according to education and marginalization levels, and access to medical care. In addition, the Age-Period-Cohort model raised, shows significant progress in terms of a downward trend in maternal mortality in a generational level. Those women born before 1980 had a greater probability of maternal death in relation to recent generations, which is a reflection of the improvement in social determinants and in the Health System. The age effect shows a problem in maternal mortality in women under 15 years old, so teen pregnancy is a priority in health and must be addressed in short term. There is no clear evidence of a period effect. PMID:29561878

Emergency Department Visits Prior to Suicide and Homicide: Linking Statewide Surveillance Systems.

PubMed

Cerel, Julie; Singleton, Michael D; Brown, Margaret M; Brown, Sabrina V; Bush, Heather M; Brancado, Candice J

2016-01-01

Emergency departments (EDs) serve a wide range of patients who present at risk of impending suicide and homicide. Two statewide surveillance systems were probabilistically linked to understand who utilizes EDs and then dies violently within 6 weeks. Each identified case was matched with four randomly selected controls on sex, race, date of birth, resident zip code, and date of ED visit vs. date of death. Matched-pair odds ratios were estimated by conditional logistic regression to assess differences between cases and controls on reported diagnoses and expected payment sources. Of 1,599 suicides and 569 homicides in the 3-year study period, 10.7% of decedents who died by suicide (mean = 13.6 days) and 8.3% who died by homicide (mean = 16.3 days) were seen in a state ED within 6 weeks prior to death. ED attendees who died by suicide were more likely to have a diagnosis of injury/ poisoning diagnosis or mental disorder and more likely to have Medicare. Those who died by homicide were more likely to have a diagnosis of injury/poisoning and less likely to have commercial insurance. It is essential for research to further explore risk factors for imminent suicide and homicide in ED patients who present for psychiatric conditions and general injuries.

Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid.

PubMed

Scallet, Andrew C; Schmued, Larry C; Johannessen, Jan N

2005-01-01

Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity.

Characteristics of Violent Deaths Among Homeless People in Maryland, 2003-2011.

PubMed

Stanley, Jennifer L; Jansson, Alexandra V; Akinyemi, Adebola A; Mitchell, Clifford S

2016-11-01

People experiencing homelessness are susceptible to many adverse health events, including violence. The purpose of this study was to provide a descriptive analysis of homeless individuals who suffered a violent death in Maryland. Characterizing these deaths will provide a basis for additional analyses that can inform violence prevention activities. This study used data from the Maryland Violent Death Reporting System to examine violent deaths of homeless people occurring from 2003 through 2011. This surveillance system collects information on all violent deaths occurring in Maryland. Victim demographics, injury and death information, precipitating circumstances contributing to deaths, and toxicology information were examined. All analyses were conducted in 2014 and 2015. Among all violent death victims from 2003 through 2011 (N=14,327), a total of 279 (2.0%) were identified as homeless victims. More than half (65.2%) of deaths were of undetermined intent, 21.2% were homicides, and 13.6% were suicides. The most common method of injury was poisoning (59.0%). Substance abuse and having a current mental health problem were among the most commonly reported circumstances relating to death. This study found substance abuse and mental health problems to be major circumstances precipitating violent death among people experiencing homelessness. This study will serve as a starting point for more in-depth analyses on experiences of violent death among homeless people that can inform violence prevention policy and programming. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Found in translation: how preclinical research is guiding the clinical development of the BCL-2-selective inhibitor venetoclax

PubMed Central

Leverson, Joel D.; Sampath, Deepak; Souers, Andrew J.; Rosenberg, Saul H.; Fairbrother, Wayne J.; Amiot, Martine; Konopleva, Marina; Letai, Anthony

2017-01-01

Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high priority goal for cancer therapy. After decades of effort, drug discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL-2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL-2 biology, were essential to the development of BH3 mimetics such as the BCL-2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL-2 biology and facilitated the clinical development of venetoclax. PMID:29146569

A stapled BIM peptide overcomes apoptotic resistance in hematologic cancers

PubMed Central

LaBelle, James L.; Katz, Samuel G.; Bird, Gregory H.; Gavathiotis, Evripidis; Stewart, Michelle L.; Lawrence, Chelsea; Fisher, Jill K.; Godes, Marina; Pitter, Kenneth; Kung, Andrew L.; Walensky, Loren D.

2012-01-01

Cancer cells subvert the natural balance between cellular life and death, achieving immortality through pathologic enforcement of survival pathways and blockade of cell death mechanisms. Pro-apoptotic BCL-2 family proteins are frequently disarmed in relapsed and refractory cancer through genetic deletion or interaction-based neutralization by overexpressed antiapoptotic proteins, resulting in resistance to chemotherapy and radiation treatments. New pharmacologic strategies are urgently needed to overcome these formidable apoptotic blockades. We harnessed the natural killing activity of BCL-2–interacting mediator of cell death (BIM), which contains one of the most potent BH3 death domains of the BCL-2 protein family, to restore BH3-dependent cell death in resistant hematologic cancers. A hydrocarbon-stapled peptide modeled after the BIM BH3 helix broadly targeted BCL-2 family proteins with high affinity, blocked inhibitory antiapoptotic interactions, directly triggered proapoptotic activity, and induced dose-responsive and BH3 sequence–specific cell death of hematologic cancer cells. The therapeutic potential of stapled BIM BH3 was highlighted by the selective activation of cell death in the aberrant lymphoid infiltrates of mice reconstituted with BIM-deficient bone marrow and in a human AML xenograft model. Thus, we found that broad and multimodal targeting of the BCL-2 family pathway can overcome pathologic barriers to cell death. PMID:22622039

[Forensic Analysis of 6 Cases of Sudden Death due to Hyperthyroid Heart Disease].

PubMed

Zhang, M Z; Li, B X; Zhao, R; Guan, D W; Zhang, G H; Wu, X; Zhu, B L; Li, R B

2017-10-01

To analyse the cases of sudden death due to hyperthyroid heart disease, and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases. Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine, China Medical University. The general information （gender and age）, clinical manifestations, medical history, anatomical and histopathological findings, biochemical parameters and cause of death were analysed retrospectively. Most of the 6 patients had definite history of hyperthyroidism, and they all showed certain degrees of symptoms of cardiovascular disease; had obvious incentive factors of death; histopathological examination of thyroid conformed to the performances of diffuse toxic goiter; with increase of cardiac weight, dilatation of cardiac chambers, myocardial hypertrophy and focal necrosis; postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease. The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy, histopathological examination, postmortem toxicology tests. The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary. Copyright© by the Editorial Department of Journal of Forensic Medicine

Dances of Death: macabre mirrors of an unequal society.

PubMed

Mackenbach, Johan Pieter; Dreier, Rolf Paul

2012-12-01

Between 1400 and 1800, Dances of Death were a popular art form depicting a metaphorical encounter between Death and representatives of a stratified human society. We review the thematic development of Dances of Death and study the development of social critique. We first assembled a full catalogue of all Dances of Death created between 1400 and 1800. We then analyzed patterns of spatiotemporal diffusion and made an in-depth hermeneutic study of the combined texts and images of a carefully selected set of 20 Dances of Death, comparing four distinct periods (1425-1525, 1525-1600, 1600-1650, and 1650-1800). We identified more than 500 Dances of Death. It was only in its first stage of development, coinciding with the Pre-Reformation (1425-1525), that social critique was very prominent. This was represented in four forms: explicit references to social (in) equality, to failures of the authorities, and to emancipated farmers, and a general social realism. In later phases social critique largely disappeared and was replaced by religious themes. Dances of Death provide historical context to current analyses and debates of social inequalities in health. They remind us of the stubbornness of these inequalities, which despite progress in material well-being are still very much with us today.

‘Hints' in the killer protein gasdermin D: unveiling the secrets of gasdermins driving cell death

PubMed Central

Qiu, Shiqiao; Liu, Jing; Xing, Feiyue

2017-01-01

Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections. Intriguingly, other gasdermin family members also share similar N-terminal domains, but they present different cell death programs. Herein, we summarize features and functions of the novel player proteins in cell death, including GSDMD triggering pyroptosis, Gsdma3/GSDMA initiating autophagy/apoptosis and DFNA5 inducing apoptosis/secondary necrosis. The gasdermin N terminus appears to be a novel pore-forming protein. This provides novel insight into the underlying roles and mechanisms of lytic or nonlytic forms of programmed cell death, as well as their potential applications in inflammation-associated diseases. PMID:28362726

Factors Associated with Increased Rates of Post-procedural Stroke or Death following Carotid Artery Stent Placement: A Systematic Review.

PubMed Central

Khan, Muhib; Qureshi, Adnan I

2014-01-01

Background and Purpose We provide an assessment of clinical, angiographic, and procedure related risk factors associated with stroke and/or death in patients undergoing carotid artery stent placement which will assist in patient stratification and identification of high-stent risk patients. Methods A comprehensive search of Medline from January 1st 1996 to December 31st 2011 was performed with key words “carotid artery stenosis”, “ carotid artery stenting”, “carotid artery stent placement”, “death” , ” mortality”, “stroke”, “outcome”, “clinical predictors”, “angiographic predictors”, was performed in various combinations. We independently abstracted data and assessed the quality of the studies. This analysis led to the selection of 71 articles for review. Results Clinical factors including age≥80 years, symptomatic status, procedure within 2 weeks of symptoms, chronic renal failure, diabetes mellitus, and hemispheric TIA were associated with stroke (ischemic or hemorrhagic) and death within 1 month after carotid artery stent placement. Angiographic factors including left carotid artery intervention, stenosis > 90%, ulcerated and calcified plaques, lesion length > 10mm, thrombus at the site, ostial involvement, predilation without EPD, ICA-CCA angulation > 60%, aortic arch type III, and aortic arch calcification were also associated with 1 month stroke and/or death. Intra-procedural platelet GP IIb/IIIa inhibitors, protamine use, multiple stents, predilatation prior to stent placement were associated with stroke (ischemic or hemorrhagic) and death after carotid artery stent placement. Intraprocedural use of embolic protection devices and stent design (open versus closed cell design) did not demonstrate a consistent relationship with 1 month stroke and/or death. Procedural statin use, and operator and center experience of more than 50 procedures per year were protective for 1 month stroke and/or death. Conclusions Our review identified risk factors for stroke, death, and MI within 1 month in patients undergoing carotid artery stent placement. Such information will result in better patient selection for carotid artery stent placement particularly in those who are also candidates for carotid endarterectomy. PMID:24920983

Completeness and reliability of mortality data in Viet Nam: Implications for the national routine health management information system

PubMed Central

Phuong Hoa, Nguyen; Walker, Sue M.; Hill, Peter S.; Rao, Chalapati

2018-01-01

Background Mortality statistics form a crucial component of national Health Management Information Systems (HMIS). However, there are limitations in the availability and quality of mortality data at national level in Viet Nam. This study assessed the completeness of recorded deaths and the reliability of recorded causes of death (COD) in the A6 death registers in the national routine HMIS in Viet Nam. Methodology and findings 1477 identified deaths in 2014 were reviewed in two provinces. A capture-recapture method was applied to assess the completeness of the A6 death registers. 1365 household verbal autopsy (VA) interviews were successfully conducted, and these were reviewed by physicians who assigned multiple and underlying cause of death (UCOD). These UCODs from VA were then compared with the CODs recorded in the A6 death registers, using kappa scores to assess the reliability of the A6 death register diagnoses. The overall completeness of the A6 death registers in the two provinces was 89.3% (95%CI: 87.8–90.8). No COD recorded in the A6 death registers demonstrated good reliability. There is very low reliability in recording of cardiovascular deaths (kappa for stroke = 0.47 and kappa for ischaemic heart diseases = 0.42) and diabetes (kappa = 0.33). The reporting of deaths due to road traffic accidents, HIV and some cancers are at a moderate level of reliability with kappa scores ranging between 0.57–0.69 (p<0.01). VA methods identify more specific COD than the A6 death registers, and also allow identification of multiple CODs. Conclusions The study results suggest that data completeness in HMIS A6 death registers in the study sample of communes was relatively high (nearly 90%), but triangulation with death records from other sources would improve the completeness of this system. Further, there is an urgent need to enhance the reliability of COD recorded in the A6 death registers, for which VA methods could be effective. Focussed consultation among stakeholders is needed to develop a suitable mechanism and process for integrating VA methods into the national routine HMIS A6 death registers in Viet Nam. PMID:29370191

Road traffic related mortality in Vietnam: Evidence for policy from a national sample mortality surveillance system

PubMed Central

2012-01-01

Background Road traffic injuries (RTIs) are among the leading causes of mortality in Vietnam. However, mortality data collection systems in Vietnam in general and for RTIs in particular, remain inconsistent and incomplete. Underlying distributions of external causes and body injuries are not available from routine data collection systems or from studies till date. This paper presents characteristics, user type pattern, seasonal distribution, and causes of 1,061 deaths attributable to road crashes ascertained from a national sample mortality surveillance system in Vietnam over a two-year period (2008 and 2009). Methods A sample mortality surveillance system was designed for Vietnam, comprising 192 communes in 16 provinces, accounting for approximately 3% of the Vietnamese population. Deaths were identified from commune level data sources, and followed up by verbal autopsy (VA) based ascertainment of cause of death. Age-standardised mortality rates from RTIs were computed. VA questionnaires were analysed in depth to derive descriptive characteristics of RTI deaths in the sample. Results The age-standardized mortality rates from RTIs were 33.5 and 8.5 per 100,000 for males and females respectively. Majority of deaths were males (79%). Seventy three percent of all deaths were aged from 15 to 49 years and 58% were motorcycle users. As high as 80% of deaths occurred on the day of injury, 42% occurred prior to arrival at hospital, and a further 29% occurred on-site. Direct causes of death were identified for 446 deaths (42%) with head injuries being the most common cause attributable to road traffic injuries overall (79%) and to motorcycle crashes in particular (78%). Conclusion The VA method can provide a useful data source to analyse RTI mortality. The observed considerable mortality from head injuries among motorcycle users highlights the need to evaluate current practice and effectiveness of motorcycle helmet use in Vietnam. The high number of deaths occurring on-site or prior to hospital admission indicates a need for effective pre-hospital first aid services and timely access to emergency facilities. In the absence of standardised death certification, sustained efforts are needed to strengthen mortality surveillance sites supplemented by VA to support evidence based monitoring and control of RTI mortality. PMID:22838959

Risk factors for fetal death after radiofrequency ablation for complicated monochorionic twin pregnancies.

PubMed

Sun, Luming; Zou, Gang; Yang, Yingjun; Zhou, Fenhe; Tao, Duan

2018-04-19

Radiofrequency ablation (RFA) is a management alternative for complicated monochorionic twin pregnancies. The purpose of this study is to evaluate risk factors for fetal death after RFA. An observational study was performed to document the perinatal outcomes of all cases undergoing fetal reduction using RFA from 2010 to 2016 at the Shanghai First Maternity and Infant Hospital. A multiple regression model was built to identify predictors of the death of the remaining fetus after RFA. A total of 183 patients treated with RFA for fetal reduction were analyzed, including 53 selective intrauterine growth restriction, 35 twin-twin transfusion syndrome, 36 dichorionic triamniotic triplets, 24 monochorionic twins discordant for fetal anomaly, and 35 twin reversed arterial perfusion. The prevalence of fetal death after RFA was 23% (43:183). The occurrence of fetal death after RFA was independently associated with more than 2 cycles of RFA coagulation (OR 3.46; 95% CI, 1.34-8.94; P = .01). More than 2 cycles of RFA coagulation is the only independent risk factors of fetal death after RFA. © 2018 John Wiley & Sons, Ltd.

The relationship between consanguineous marriage and death in fetus and infants.

PubMed

Mohammadi, Majid Mehr; Hooman, Heidar Ali; Afrooz, Gholam Ali; Daramadi, Parviz Sharifi

2012-05-01

Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages.

Surveillance of US Death Rates from Chronic Diseases Related to Excessive Alcohol Use.

PubMed

Polednak, Anthony P

2016-01-01

To assess the utility of multiple-cause (MC) death records for surveillance of US mortality rates from chronic causes related to excessive alcohol use. The Alcohol-Related Disease Impact (ARDI) resource produced estimates of the population 'alcohol attributable fraction' (AAF) due to excessive drinking for each alcohol-related (AAF > 0%) cause of death, and used AAFs to estimate numbers of alcohol-related deaths from alcohol-related underlying causes (UC) in adults age 20-64 and 65+ years in 2006-2010. For surveillance, this study used MC death file to identify individual deaths (2006-2010) with an 'alcohol-induced' cause (AAF = 100%) anywhere on the certificate, and to obtain US rates of premature death (ages 15-64 and 65-74 years) for 1999-2012. Using the selected MC records, numbers of deaths from alcohol-related chronic UC (2006-2010) were 81% of ARDI estimates for age 20-64, but only 40% for 65+ years. The MC records identified substantial numbers of deaths from causes (e.g. certain infectious diseases) not included as alcohol-related in ARDI, but included in surveillance of premature death rates for chronic UC. Also, premature death rates for chronic alcohol-induced causes using only the UC (as in routine mortality statistics) were only about half the rates based on MC; all rates increased in recent years but some reached statistical significance only by using MC. Using MC records underestimated total US deaths from alcohol-related chronic causes as the UC, but enhanced surveillance of rates for premature deaths involving chronic causes that may be related to excessive alcohol use. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

5 CFR 843.310 - Annuity based on death of an employee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Annuity based on death of an employee... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.310 Annuity based on death of an employee. Except as provided in...

5 CFR 843.311 - Annuity based on death of a separated employee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... beginning on the day after the death of the separated employee. (ii) The rate of the adjusted annuity equals... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Annuity based on death of a separated... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS...

5 CFR 843.311 - Annuity based on death of a separated employee.

Code of Federal Regulations, 2012 CFR

2012-01-01

... beginning on the day after the death of the separated employee. (ii) The rate of the adjusted annuity equals... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Annuity based on death of a separated... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS...

5 CFR 843.311 - Annuity based on death of a separated employee.

Code of Federal Regulations, 2011 CFR

2011-01-01

... beginning on the day after the death of the separated employee. (ii) The rate of the adjusted annuity equals... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Annuity based on death of a separated... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS...

5 CFR 843.311 - Annuity based on death of a separated employee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... beginning on the day after the death of the separated employee. (ii) The rate of the adjusted annuity equals... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Annuity based on death of a separated... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS...

5 CFR 843.311 - Annuity based on death of a separated employee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... beginning on the day after the death of the separated employee. (ii) The rate of the adjusted annuity equals... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Annuity based on death of a separated... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS...

5 CFR 843.310 - Annuity based on death of an employee.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Annuity based on death of an employee... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.310 Annuity based on death of an employee. Except as provided in...

5 CFR 843.310 - Annuity based on death of an employee.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Annuity based on death of an employee... SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES RETIREMENT SYSTEM-DEATH BENEFITS AND EMPLOYEE REFUNDS Current and Former Spouse Benefits § 843.310 Annuity based on death of an employee. Except as provided in...

Young, Black, and Sentenced To Die: Black Males and the Death Penalty.

ERIC Educational Resources Information Center

Joseph, Janice

1996-01-01

Explores the death penalty as imposed on young black males in the United States and examines the disparity in death penalty rates for homicides with black offenders and white victims. States continue to impose the death penalty rather than viewing youth violence as a failure of the social system. (SLD)

Exophiala angulospora Causes Systemic Mycosis in Atlantic Halibut: a Case Report.

PubMed

Overy, David P; Groman, David; Giles, Jan; Duffy, Stephanie; Rommens, Mellisa; Johnson, Gerald

2015-03-01

Filamentous black yeasts from the genus Exophiala are ubiquitous, opportunistic pathogens causing both superficial and systemic mycoses in warm- and cold-blooded animals. Infections by black yeasts have been reported relatively frequently in a variety of captive and farmed freshwater and marine fishes. In November 2012, moribund and recently dead, farm-raised Atlantic Halibut Hippoglossus hippoglossus were necropsied to determine the cause of death. Histopathology revealed that three of seven fish were affected by a combination of an ascending trans-ductual granulomatous mycotic nephritis, necrotizing histiocytic encephalitis, and in one fish the addition of a fibrogranulomatous submucosal branchitis. Microbial cultures of kidney using selective mycotic media revealed pure growth of a black-pigmenting septated agent. Application of molecular and phenotypic taxonomy methodologies determined that all three isolates were genetically consistent with Exophiala angulospora. This is the first report of E. angulospora as the causal agent of systemic mycosis in Atlantic Halibut.

NASA Dryden test pilot Michael J. Adams

NASA Image and Video Library

1967-03-22

Air Force test pilot Maj. Michael J. Adams stands beside X-15 ship number one. Adams was selected for the X-15 program in 1966 and made his first flight on Oct. 6, 1966. On Nov. 15, 1967, Adams made his seventh and final X-15 flight. The X-15 launched from the B-52, but during the ascent an electrical problem affected the X-15's control system. The aircraft crashed northwest of Cuddeback Lake, California, causing the death of Adams. He was posthumously awarded Air Force astronaut wings because his final flight exceeded 50 miles in altitude. Adams was the only pilot lost in the 199-flight X-15 program.

Deaths on board ships assisted by the Centro Internazionale Radio Medico in the last 25 years.

PubMed

Grappasonni, Iolanda; Petrelli, Fabio; Amenta, Francesco

2012-07-01

Data on occupational diseases of seafarers and of causes of death during their career are sparse. The causes of deaths on board ships assisted by Centro Internazionale Radio Medico (CIRM), the Italian Telemedical Maritime Assistance Service (TMAS) were reviewed by examining 29,146 files of patients treated from 1986 to 2010. In the 25 years, 383 deaths occurred (1.31%). Diseases of the circulation were the most frequent, followed by external causes such as accidents and violence, infectious and parasitic diseases, alcohol and drug addiction, respiratory system diseases. Cardiovascular and external causes were the principal causes of deaths among seafarers. This investigation is the first study on the causes of death on board ships obtained from data of a maritime telemedical centre, that has assisted seafarers when they were alive or immediately after their death. The fact that diseases of the circulatory system are the first cause of death of sailing seafarers deserves specific initiatives. They should include campaigns for adequate lifestyles and the availability on ships of medical devices useful for diagnostic purposes, resuscitation as well as for verification of death. Copyright © 2012 Elsevier Ltd. All rights reserved.

77 FR 76299 - Towing Safety Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-27

... system (AIS), and plans to improve Coast Guard Form 2692 for reporting a marine accident, injury or death... System (AIS), and (c) Plans to improve Coast Guard Form 2692, REPORT OF MARINE ACCIDENT, INJURY OR DEATH...

Optimising the dichotomy limit for left ventricular ejection fraction in selecting patients for defibrillator therapy after myocardial infarction.

PubMed

Yap, Yee Guan; Duong, Trinh; Bland, J Martin; Malik, Marek; Torp-Pedersen, Christian; Køber, Lars; Gallagher, Mark M; Camm, A John

2007-07-01

The selection of patients for prophylactic implantable cardioverter-defibrilator (ICD) treatment after myocardial infarction (MI) remains controversial. To determine the optimum left ventricular ejection fraction (LVEF) dichotomy limit for ICD treatment in patients with a history of MI. Data from the placebo arms of four randomised trials were pooled to create a cohort of 2828 patients (2206 men, mean (SD) age 65 (11) years) with reduced left ventricular function after MI. The median LVEF was 33% (range 6-40%). LVEF significantly predicted mortality. Each 10% reduction in LVEF <40% conferred a 42% increase in all-cause mortality, a 39% increase in arrhythmic cardiac mortality and a 49% increase in non-arrhythmic cardiac mortality over the 2-year period of follow-up (p<0.001 for all modes of mortality). As the LVEF progressively decreased from < or =40% to < or =10%, the data show a U-shaped relationship between the dichotomy limit for LVEF used and the number of patients who must be treated to prevent one arrhythmic death in 2 years. At an LVEF of 16-20%, more patients are likely to die from arrhythmic than non-arrhythmic cardiac deaths, whereas in those with LVEF < or =10% all deaths were non-arrhythmic. However, the total number of deaths substantially decreased with lower LVEF. A trade-off exists between the sensitivity and positive predictive accuracy across a range of LVEF, and no single dichotomy limit is completely satisfactory. In patients with LVEF < or =10% ICD treatment was not beneficial as all patients in this subgroup died from non-arrhythmic causes. The use of a single dichotomy limit for LVEF alone is not sufficient in selecting patients for ICD treatment in the primary prevention of cardiac arrest.

A method for evaluating the importance of system state observations to model predictions, with application to the Death Valley regional groundwater flow system

USGS Publications Warehouse

Tiedeman, Claire; Ely, D. Matthew; Hill, Mary C.; O'Brien, Grady M.

2004-01-01

We develop a new observation‐prediction (OPR) statistic for evaluating the importance of system state observations to model predictions. The OPR statistic measures the change in prediction uncertainty produced when an observation is added to or removed from an existing monitoring network, and it can be used to guide refinement and enhancement of the network. Prediction uncertainty is approximated using a first‐order second‐moment method. We apply the OPR statistic to a model of the Death Valley regional groundwater flow system (DVRFS) to evaluate the importance of existing and potential hydraulic head observations to predicted advective transport paths in the saturated zone underlying Yucca Mountain and underground testing areas on the Nevada Test Site. Important existing observations tend to be far from the predicted paths, and many unimportant observations are in areas of high observation density. These results can be used to select locations at which increased observation accuracy would be beneficial and locations that could be removed from the network. Important potential observations are mostly in areas of high hydraulic gradient far from the paths. Results for both existing and potential observations are related to the flow system dynamics and coarse parameter zonation in the DVRFS model. If system properties in different locations are as similar as the zonation assumes, then the OPR results illustrate a data collection opportunity whereby observations in distant, high‐gradient areas can provide information about properties in flatter‐gradient areas near the paths. If this similarity is suspect, then the analysis produces a different type of data collection opportunity involving testing of model assumptions critical to the OPR results.

Knowledge of the Brain Death Concept Among the Population of Havana, Cuba.

PubMed

Ríos, A; López-Navas, A I; Sánchez, Á; Martinez-Alarcon, L; Ayala, M A; Garrido, G; Sebastián, M J; Ramis, G; Abdo-Cuza, A; Hernández, A; Ramírez, P; Parrilla, P

2018-03-01

One of the main reasons against organ donation is the fear of apparent death due to ignorance of the brain death concept. Our aim was to assess knowledge about and acceptance of the brain death concept among the population of Havana, Cuba. The population screened, stratified by gender and age, included those >15 years old and living in Havana, Cuba. The appraisal tool utilized was a questionnaire on attitude toward organ donation ("PCID-DTO Ríos"). A random selection of individuals were surveyed according to the stratification. Cuba's census data were used. The participation was anonymized and self-administered. The verbal consent of participants was provided. There were 920 respondents: 31% (n = 282) knew the concept of brain death and accepted it; 57% (n = 529) did not; and 12% (n = 109) had a misperception, or did not accept brain death as a person's death. Those who knew and accepted the concept had a more favorable attitude toward their own organ donation after death (85% vs 61%; P < .001). The psychosocial factors related to the knowledge of brain death concept were: the gender (P = .002), to make up for speaking at a family level about the organ transplant (P < .001), the couple's opinion about the organ donation (P < .001) and the religion (P < .001). The brain death concept is not well understood in the population of Havana, Cuba. Copyright © 2017 Elsevier Inc. All rights reserved.

Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in Metropolitan and Nonmetropolitan Areas - United States.

PubMed

Mack, Karin A; Jones, Christopher M; Ballesteros, Michael F

2017-10-20

Drug overdoses are a leading cause of injury death in the United States, resulting in approximately 52,000 deaths in 2015. Understanding differences in illicit drug use, illicit drug use disorders, and overall drug overdose deaths in metropolitan and nonmetropolitan areas is important for informing public health programs, interventions, and policies. Illicit drug use and drug use disorders during 2003-2014, and drug overdose deaths during 1999-2015. The National Survey of Drug Use and Health (NSDUH) collects information through face-to-face household interviews about the use of illicit drugs, alcohol, and tobacco among the U.S. noninstitutionalized civilian population aged ≥12 years. Respondents include residents of households and noninstitutional group quarters (e.g., shelters, rooming houses, dormitories, migratory workers' camps, and halfway houses) and civilians living on military bases. NSDUH variables include sex, age, race/ethnicity, residence (metropolitan/nonmetropolitan), annual household income, self-reported drug use, and drug use disorders. National Vital Statistics System Mortality (NVSS-M) data for U.S. residents include information from death certificates filed in the 50 states and the District of Columbia. Cases were selected with an underlying cause of death based on the ICD-10 codes for drug overdoses (X40-X44, X60-X64, X85, and Y10-Y14). NVSS-M variables include decedent characteristics (sex, age, and race/ethnicity) and information on intent (unintentional, suicide, homicide, or undetermined), location of death (medical facility, in a home, or other [including nursing homes, hospices, unknown, and other locations]) and county of residence (metropolitan/nonmetropolitan). Metropolitan/nonmetropolitan status is assigned independently in each data system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of ≥1 million persons; CBSA of <1 million persons; and not a CBSA, which for simplicity were labeled large metropolitan, small metropolitan, and nonmetropolitan. Deaths from NVSS-M are categorized by the county of residence of the decedent using CDC's National Center for Health Statistics 2013 Urban-Rural Classification Scheme, collapsed into two categories (metropolitan and nonmetropolitan). Although both metropolitan and nonmetropolitan areas experienced significant increases from 2003-2005 to 2012-2014 in self-reported past-month use of illicit drugs, the prevalence was highest for the large metropolitan areas compared with small metropolitan or nonmetropolitan areas throughout the study period. Notably, past-month use of illicit drugs declined over the study period for the youngest respondents (aged 12-17 years). The prevalence of past-year illicit drug use disorders among persons using illicit drugs in the past year varied by metropolitan/nonmetropolitan status and changed over time. Across both metropolitan and nonmetropolitan areas, the prevalence of past-year illicit drug use disorders declined during 2003-2014. In 2015, approximately six times as many drug overdose deaths occurred in metropolitan areas than occurred in nonmetropolitan areas (metropolitan: 45,059; nonmetropolitan: 7,345). Drug overdose death rates (per 100,000 population) for metropolitan areas were higher than in nonmetropolitan areas in 1999 (6.4 versus 4.0), however, the rates converged in 2004, and by 2015, the nonmetropolitan rate (17.0) was slightly higher than the metropolitan rate (16.2). Drug use and subsequent overdoses continue to be a critical and complicated public health challenge across metropolitan/nonmetropolitan areas. The decline in illicit drug use by youth and the lower prevalence of illicit drug use disorders in rural areas during 2012-2014 are encouraging signs. However, the increasing rate of drug overdose deaths in rural areas, which surpassed rates in urban areas, is cause for concern. Understanding the differences between metropolitan and nonmetropolitan areas in drug use, drug use disorders, and drug overdose deaths can help public health professionals to identify, monitor, and prioritize responses. Consideration of where persons live and where they die from overdose could enhance specific overdose prevention interventions, such as training on naloxone administration or rescue breathing. Educating prescribers on CDC's guideline for prescribing opioids for chronic pain (Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. MMWR Recomm Rep 2016;66[No. RR-1]) and facilitating better access to medication-assisted treatment with methadone, buprenorphine, or naltrexone could benefit communities with high opioid use disorder rates.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Can Statewide Emergency Department, Hospital Discharge, and Violent Death Reporting System Data Be Used to Monitor Burden of Firearm-Related Injury and Death in Rhode Island?

PubMed

Jiang, Yongwen; Ranney, Megan L; Sullivan, Brian; Hilliard, Dennis; Viner-Brown, Samara; Alexander-Scott, Nicole

2018-03-07

National data on the epidemiology of firearm injuries and circumstances of firearm deaths are difficult to obtain and often are nonreliable. Since firearm injury and death rates and causes can vary substantially between states, it is critical to consider state-specific data sources. In this study, we illustrate how states can systematically examine demographic characteristics, firearm information, type of wound, toxicology tests, precipitating circumstances, and costs to provide a comprehensive picture of firearm injuries and deaths using data sets from a single state with relatively low rates of firearm injury and death. Cross-sectional study. Firearm-related injury data for the period 2005-2014 were obtained from the Rhode Island emergency department and hospital discharge data sets; death data for the same period were obtained from the Rhode Island Violent Death Reporting System. Descriptive statistics were used. Healthcare Cost and Utilization Project cost-to-charge ratios were used to convert total hospital charges to costs. Most firearm-related emergency department visits (55.8%) and hospital discharges (79.2%) in Rhode Island were from assaults; however, most firearm-related deaths were suicides (60.1%). The annual cost of firearm-related hospitalizations was more than $830 000. Most decedents who died because of firearms tested positive for illicit substances. Nearly a quarter (23.5%) of firearm-related homicides were due to a conflict between the decedent and suspect. More than half (59%) of firearm suicide decedents were reported to have had current mental or physical problems prior to death. Understanding the state-specific magnitude and patterns (who, where, factors, etc) of firearm injury and death may help inform local injury prevention efforts. States with similar data sets may want to adopt our analyses. Surveillance of firearm-related injury and death is essential. Dissemination of surveillance findings to key stakeholders is critical in improving firearm injury prevention. States that are not part of the National Violent Death Reporting System (NVDRS) could work with their other data sources to obtain a better picture of violent injuries and deaths to make the best use of resources.

Place of death of children with complex chronic conditions: cross-national study of 11 countries.

PubMed

Håkanson, Cecilia; Öhlén, Joakim; Kreicbergs, Ulrika; Cardenas-Turanzas, Marylou; Wilson, Donna M; Loucka, Martin; Frache, Sandra; Giovannetti, Lucia; Naylor, Wayne; Rhee, YongJoo; Ramos, Miguel Ruiz; Teno, Joan; Beernaert, Kim; Deliens, Luc; Houttekier, Dirk; Cohen, Joachim

2017-03-01

Cross-national understanding of place of death is crucial for health service systems for their provision of efficient and equal access to paediatric palliative care. The objectives of this population-level study were to examine where children with complex chronic conditions (CCC) die and to investigate associations between places of death and sex, cause of death and country. The study used death certificate data of all deceased 1- to 17-year-old children (n = 40,624) who died in 2008, in 11 European and non-European countries. Multivariable logistic regression was performed to determine associations between place of death and other factors. Between 24.4 and 75.3% of all children 1-17 years in the countries died of CCC. Of these, between 6.7 and 42.4% died at home. In Belgium and the USA, all deaths caused by CCC other than malignancies were less likely to occur at home, whereas in Mexico and South Korea, deaths caused by neuromuscular diseases were more likely to occur at home than malignancies. In Mexico (OR = 0.91, 95% CI: 0.83-1.00) and Sweden (OR = 0.35, 95% CI: 0.15-0.83), girls had a significantly lower chance of dying at home than boys. This study shows large cross-national variations in place of death. These variations may relate to health system-related infrastructures and policies, and differences in cultural values related to place of death, although this needs further investigation. The patterns found in this study can inform the development of paediatric palliative care programs internationally. What is known: • There is a scarcity of population-level studies investigating where children with CCC die in different countries. • Cross-national understanding of place of death provides information to health care systems for providing efficient and equal access to paediatric palliative care. What is new : • There are large cross-national variations in the place of death of children with CCC, with few deathsoccuring at home in some countries whereas hospital deaths are generally most common. • In general, deaths caused by neuromuscular diseases and malignancies occur at home more often thanother CCC.

Childhood Maltreatment, Public Service System Contact, and Preventable Death in Young Adulthood.

PubMed

Jonson-Reid, Melissa; Drake, Brett; Kohl, Patricia L

2017-02-01

Data from a longitudinal cohort study of low-income children reported for maltreatment matched to similarly poor nonreported children were used to examine intentional and unintentional injury deaths in young adulthood. The goal was to examine the unique contribution of maltreatment history and identify other potential systems for preventive efforts. Maltreatment reports were associated with increased risk of injury-related death per 6-month intervals (hazard ratio [HR] = 1.09, p < .05). Young adults with histories of both status offenses and delinquent offenses were at greater risk for later death (HR = 2.24, p < .05) as were those with histories of emergency room (ER) treatment for intentional injury prior to age 18 years (HR =3.95, p < .05). More than 50% of the deaths were firearm-related; nearly all firearm deaths occurred among Black youth. Implications for prevention within at-risk populations are discussed.

Regulation of alveolar macrophage death in acute lung inflammation.

PubMed

Fan, Erica K Y; Fan, Jie

2018-03-27

Acute lung injury (ALI) and its severe form, known as acute respiratory distress syndrome (ARDS), are caused by direct pulmonary insults and indirect systemic inflammatory responses that result from conditions such as sepsis, trauma, and major surgery. The reciprocal influences between pulmonary and systemic inflammation augments the inflammatory process in the lung and promotes the development of ALI. Emerging evidence has revealed that alveolar macrophage (AM) death plays important roles in the progression of lung inflammation through its influence on other immune cell populations in the lung. Cell death and tissue inflammation form a positive feedback cycle, ultimately leading to exaggerated inflammation and development of disease. Pharmacological manipulation of AM death signals may serve as a logical therapeutic strategy for ALI/ARDS. This review will focus on recent advances in the regulation and underlying mechanisms of AM death as well as the influence of AM death on the development of ALI.

Unintentional firearm deaths: a comparison of other-inflicted and self-inflicted shootings.

PubMed

Hemenway, David; Barber, Catherine; Miller, Matthew

2010-07-01

This study compares other-inflicted and self-inflicted unintentional firearm fatalities. Data come from the National Violent Death Reporting System, a new surveillance system from the Centers for Disease Control and Prevention. Data are currently available from 16 states and parts of California for various years 2003-2006. Of the 363 unintentional firearm fatalities, about half (49%) were other-inflicted, ranging from 78% of child (aged 0-14) deaths to 19% of older adult (aged 55+) deaths. In other-inflicted shooting deaths, the shooters were overwhelmingly young (81% under age 25). The shooters in the other-inflicted deaths were primarily friends (43%) or family (47%); brothers were the most common family shooter. To learn how to prevent unintentional injuries, it is critical to have information not only on the victim, but also on the person who inflicted the injury. Copyright 2010 Elsevier Ltd. All rights reserved.

Community-based measles mortality surveillance in two districts of Katanga Province, Democratic Republic of Congo.

PubMed

N'goran, Alexandra A; Ilunga, Ngoie; Coldiron, Matthew E; Grais, Rebecca F; Porten, Klaudia

2013-12-17

Mortality due to measles is often under-reported. Traditional methods of measuring mortality can be time and resource-intensive. We describe the implementation of a community-based method to monitor measles mortality. Using standardized questionnaires in the midst of a measles outbreak, a community-based network of volunteers recorded a much larger number of deaths (376) than deaths recorded in health centres (27). Deaths were predominantly (93.5%) among children aged less than 5 years; 54.5% of measles deaths reported antecedent measles vaccination. In this setting, the number of deaths due to measles reported in community-based surveillance was much higher than deaths reported in health centres. Lack of reliable population data and incomplete coverage of the surveillance system make it impossible to calculate overall attack rates and cause-specific mortality rates. Similar systems could be rapidly implemented in other difficult outbreak settings.

Fight or Flight - Regulation of Emergency Hematopoiesis by Pyroptosis and Necroptosis

PubMed Central

Croker, Ben A.; Silke, John; Gerlic, Motti

2015-01-01

Purpose of review A feature of the innate immune response that is conserved across kingdoms is the induction of cell death. In this review, we discuss the direct and indirect effects of increased inflammatory cell death, including pyroptosis, a caspase-1-dependent cell death, and necroptosis, a RIPK3/MLKL-dependent, caspase-independent cell death, on emergency hematopoiesis. Recent findings Activation of non-apoptotic cell death pathways during infection can trigger release of cytokines and/or damage-associated molecular patterns (DAMPs) such as IL-1α, IL-1β, IL-18, IL-33, HMGB1 and mtDNA to promote emergency hematopoiesis. During systemic infection, pyroptosis and necroptosis can directly kill hematopoietic stem and progenitor cells, which results in impaired hematopoiesis, cytopenia and immunosuppression. Although originally described as discrete entities, there now appears to be more intimate connections between the non-apoptotic and death receptor signaling pathways. Summary The choice to undergo pyroptotic and necroptotic cell death constitutes a rapid response system serving to eliminate infected cells, including hematopoietic stem and progenitor cells. This system has the potential to be detrimental to emergency hematopoiesis during severe infection. We discuss the potential of pharmacological intervention for the pyroptosis and necroptosis pathways that may be beneficial during periods of infection and emergency hematopoiesis. PMID:26049749

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

PubMed

Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

Mithramycin is a gene-selective Sp1 inhibitor that identifies a biological intersection between cancer and neurodegeneration.

PubMed

Sleiman, Sama F; Langley, Brett C; Basso, Manuela; Berlin, Jill; Xia, Li; Payappilly, Jimmy B; Kharel, Madan K; Guo, Hengchang; Marsh, J Lawrence; Thompson, Leslie Michels; Mahishi, Lata; Ahuja, Preeti; MacLellan, W Robb; Geschwind, Daniel H; Coppola, Giovanni; Rohr, Jürgen; Ratan, Rajiv R

2011-05-04

Oncogenic transformation of postmitotic neurons triggers cell death, but the identity of genes critical for degeneration remain unclear. The antitumor antibiotic mithramycin prolongs survival of mouse models of Huntington's disease in vivo and inhibits oxidative stress-induced death in cortical neurons in vitro. We had correlated protection by mithramycin with its ability to bind to GC-rich DNA and globally displace Sp1 family transcription factors. To understand how antitumor drugs prevent neurodegeneration, here we use structure-activity relationships of mithramycin analogs to discover that selective DNA-binding inhibition of the drug is necessary for its neuroprotective effect. We identify several genes (Myc, c-Src, Hif1α, and p21(waf1/cip1)) involved in neoplastic transformation, whose altered expression correlates with protective doses of mithramycin or its analogs. Most interestingly, inhibition of one these genes, Myc, is neuroprotective, whereas forced expression of Myc induces Rattus norvegicus neuronal cell death. These results support a model in which cancer cell transformation shares key genetic components with neurodegeneration.

Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy.

PubMed

Simon, Christian M; Dai, Ya; Van Alstyne, Meaghan; Koutsioumpa, Charalampia; Pagiazitis, John G; Chalif, Joshua I; Wang, Xiaojian; Rabinowitz, Joseph E; Henderson, Christopher E; Pellizzoni, Livio; Mentis, George Z

2017-12-26

The hallmark of spinal muscular atrophy (SMA), an inherited disease caused by ubiquitous deficiency in the SMN protein, is the selective degeneration of subsets of spinal motor neurons. Here, we show that cell-autonomous activation of p53 occurs in vulnerable but not resistant motor neurons of SMA mice at pre-symptomatic stages. Moreover, pharmacological or genetic inhibition of p53 prevents motor neuron death, demonstrating that induction of p53 signaling drives neurodegeneration. At late disease stages, however, nuclear accumulation of p53 extends to resistant motor neurons and spinal interneurons but is not associated with cell death. Importantly, we identify phosphorylation of serine 18 as a specific post-translational modification of p53 that exclusively marks vulnerable SMA motor neurons and provide evidence that amino-terminal phosphorylation of p53 is required for the neurodegenerative process. Our findings indicate that distinct events induced by SMN deficiency converge on p53 to trigger selective death of vulnerable SMA motor neurons. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Spinal cord-specific deletion of the glutamate transporter GLT1 causes motor neuron death in mice.

PubMed

Sugiyama, Kaori; Tanaka, Kohichi

2018-03-04

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder characterized by the selective loss of motor neurons. The precise mechanisms that cause the selective death of motor neurons remain unclear, but a growing body of evidence suggests that glutamate-mediated excitotoxicity has been considered to play an important role in the mechanisms of motor neuron degeneration in ALS. Reductions in glutamate transporter GLT1 have been reported in animal models of ALS and the motor cortex and spinal cord of ALS patients. However, it remains unknown whether the reduction in GLT1 has a primary role in the induction of motor neuron degeneration in ALS. Here, we generated conditional knockout mice that lacked GLT1 specifically in the spinal cord by crossing floxed-GLT1 mice and Hoxb8-Cre mice. Hoxb8-Cre/GLT1 flox/flox mice showed motor deficits and motor neuron loss. Thus, loss of the glial glutamate transporter GLT1 is sufficient to cause motor neuron death in mice. Copyright © 2018 Elsevier Inc. All rights reserved.

How Does Plasma Activated Media Treatment Differ From Direct Cold Plasma Treatment.

PubMed

Attri, Pankaj; Park, Ji Hoon; Ali, Anser; Choi, Eun Ha

2018-04-06

The aim of the paper is to investigate the optimum condition for generation of plasma activated media (PAM), where it can deactivate the cancer cells while minimum damage for normal cells. Over past few years, cold atmospheric plasma-activated media (PAM) have shown its promising application in plasma medicine for treatment of cancer. PAM has a tremendous ability for selective anti-cancer capacity in vitro and in vivo. We have analyzed the radicals in air using the optical emission spectroscopy and in culture media using chemical analysis. Further, we have tested the toxicity of PAM using MTT assay. We observed that more cancer cell death is for the Ar plasma followed by the Ar-N2 plasma, and the least cell death was observed for the Ar-O2 plasma at all treatment times both by direct treatment and through PAM treatment. The concentration of the RNS species is high for Ar-N2 plasma in gas as well as inside the culture media compared to that for pure Ar plasma. However, the difference is significantly less between the Ar plasma treatments and the Ar-N2 plasma treatments, showing that ROS is the main factor contributing to cell death. Among all three feeding gas plasmas the best system is Ar-O2 plasma for direct treatments towards the cancer cells. In addition, the best system for PAM preparation is Ar-N2 at low time treatments (1 min and 2 min) because it has no effect on normal cells, but kills the cancer cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improved survival with renal transplantation for end-stage renal disease due to granulomatosis with polyangiitis: data from the United States Renal Data System.

PubMed

Wallace, Zachary S; Wallwork, Rachel; Zhang, Yuqing; Lu, Na; Cortazar, Frank; Niles, John L; Heher, Eliot; Stone, John H; Choi, Hyon K

2018-05-14

Renal transplantation is the optimal treatment for selected patients with end-stage renal disease (ESRD). However, the survival benefit of renal transplantation among patients with ESRD attributed to granulomatosis with polyangiitis (GPA) is unknown. We identified patients from the United States Renal Data System with ESRD due to GPA (ESRD-GPA) between 1995 and 2014. We restricted our analysis to waitlisted subjects to evaluate the impact of transplantation on mortality. We followed patients until death or the end of follow-up. We compared the relative risk (RR) of all-cause and cause-specific mortality in patients who received a transplant versus non-transplanted patients using a pooled logistic regression model with transplantation as a time-varying exposure. During the study period, 1525 patients were waitlisted and 946 received a renal transplant. Receiving a renal transplant was associated with a 70% reduction in the risk of all-cause mortality in multivariable-adjusted analyses (RR=0.30, 95% CI 0.25 to 0.37), largely attributed to a 90% reduction in the risk of death due to cardiovascular disease (CVD) (RR=0.10, 95% 0.06-0.16). Renal transplantation is associated with a significant decrease in all-cause mortality among patients with ESRD attributed to GPA, largely due to a decrease in the risk of death to CVD. Prompt referral for transplantation is critical to optimise outcomes for this patient population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Withaferin A Induces Cell Death Selectively in Androgen-Independent Prostate Cancer Cells but Not in Normal Fibroblast Cells

PubMed Central

Nishikawa, Yukihiro; Okuzaki, Daisuke; Fukushima, Kohshiro; Mukai, Satomi; Ohno, Shouichi; Ozaki, Yuki; Yabuta, Norikazu; Nojima, Hiroshi

2015-01-01

Withaferin A (WA), a major bioactive component of the Indian herb Withania somnifera, induces cell death (apoptosis/necrosis) in multiple types of tumor cells, but the molecular mechanism underlying this cytotoxicity remains elusive. We report here that 2 μM WA induced cell death selectively in androgen-insensitive PC-3 and DU-145 prostate adenocarcinoma cells, whereas its toxicity was less severe in androgen-sensitive LNCaP prostate adenocarcinoma cells and normal human fibroblasts (TIG-1 and KD). WA also killed PC-3 cells in spheroid-forming medium. DNA microarray analysis revealed that WA significantly increased mRNA levels of c-Fos and 11 heat-shock proteins (HSPs) in PC-3 and DU-145, but not in LNCaP and TIG-1. Western analysis revealed increased expression of c-Fos and reduced expression of the anti-apoptotic protein c-FLIP(L). Expression of HSPs such as HSPA6 and Hsp70 was conspicuously elevated; however, because siRNA-mediated depletion of HSF-1, an HSP-inducing transcription factor, reduced PC-3 cell viability, it is likely that these heat-shock genes were involved in protecting against cell death. Moreover, WA induced generation of reactive oxygen species (ROS) in PC-3 and DU-145, but not in normal fibroblasts. Immunocytochemistry and immuno-electron microscopy revealed that WA disrupted the vimentin cytoskeleton, possibly inducing the ROS generation, c-Fos expression and c-FLIP(L) suppression. These observations suggest that multiple events followed by disruption of the vimentin cytoskeleton play pivotal roles in WA-mediated cell death. PMID:26230090

[A comparison of the causes of adult mortality and its effects on life-expectancy across the regions of Colombia].

PubMed

López, Elizabeth; Arce, Patricia

2008-09-01

When determining some populations state of health, an understanding of the causes of mortality is essential. Changes in mortality due to causes was established to determine their contribution to the life-expectancy by gender and region of the Colombian population aged 15 to 74, between 1985 and 1999, by gender and region. This was a descriptive, retrospective study; the sources of information were records of deaths from 1983 to 2001 and population projections according to Departamento Administrativo Nacional de Estadística. The age selected as a sample population was 15 to 74. Changes in mortality were measured by using Eduardo Arriagas methodology, which is based on calculating temporary life-expectancy, absolute and relative change indices, and how changes in mortality due to cause of death contribute to life-expectancy. The main cause of reduced temporary life-expectancy in both genders was the increase in deaths by suicide, homicide and other violent causes (the reduction was greater for men than women in all regions studied). The greatest positive contribution to longevity was by the reduction in circulatory system diseases and accidents. A minimal gain in temporary life-expectancy was achieved as the positive affect of reduced mortality due to natural causes. This gain was annulled by the negative contributions of increased mortality due to suicide, homicide and other violent avoidable acts.

Topological control of life and death in non-proliferative epithelia.

PubMed

Martinand-Mari, Camille; Maury, Benoit; Rousset, François; Sahuquet, Alain; Mennessier, Gérard; Rochal, Sergei; Lorman, Vladimir; Mangeat, Paul; Baghdiguian, Stephen

2009-01-01

Programmed cell death is one of the most fascinating demonstrations of the plasticity of biological systems. It is classically described to act upstream of and govern major developmental patterning processes (e.g. inter-digitations in vertebrates, ommatidia in Drosophila). We show here the first evidence that massive apoptosis can also be controlled and coordinated by a pre-established pattern of a specific 'master cell' population. This new concept is supported by the development and validation of an original model of cell patterning. Ciona intestinalis eggs are surrounded by a three-layered follicular organization composed of 60 elongated floating extensions made of as many outer and inner cells, and indirectly spread through an extracellular matrix over 1200 test cells. Experimental and selective ablation of outer and inner cells results in the abrogation of apoptosis in respective remaining neighbouring test cells. In addition incubation of outer/inner follicular cell-depleted eggs with a soluble extract of apoptotic outer/inner cells partially restores apoptosis to apoptotic-defective test cells. The 60 inner follicular cells were thus identified as 'apoptotic master' cells which collectively are induction sites for programmed cell death of the underlying test cells. The position of apoptotic master cells is controlled by topological constraints exhibiting a tetrahedral symmetry, and each cell spreads over and can control the destiny of 20 smaller test cells, which leads to optimized apoptosis signalling.

High maternal mortality in Jigawa State, Northern Nigeria estimated using the sisterhood method.

PubMed

Sharma, Vandana; Brown, Willa; Kainuwa, Muhammad Abdullahi; Leight, Jessica; Nyqvist, Martina Bjorkman

2017-06-02

Maternal mortality is extremely high in Nigeria. Accurate estimation of maternal mortality is challenging in low-income settings such as Nigeria where vital registration is incomplete. The objective of this study was to estimate the lifetime risk (LTR) of maternal death and the maternal mortality ratio (MMR) in Jigawa State, Northern Nigeria using the Sisterhood Method. Interviews with 7,069 women aged 15-49 in 96 randomly selected clusters of communities in 24 Local Government Areas (LGAs) across Jigawa state were conducted. A retrospective cohort of their sisters of reproductive age was constructed to calculate the lifetime risk of maternal mortality. Using most recent estimates of total fertility for the state, the MMR was estimated. The 7,069 respondents reported 10,957 sisters who reached reproductive age. Of the 1,026 deaths in these sisters, 300 (29.2%) occurred during pregnancy, childbirth or within 42 days after delivery. This corresponds to a LTR of 6.6% and an estimated MMR for the study areas of 1,012 maternal deaths per 100,000 live births (95% CI: 898-1,126) with a time reference of 2001. Jigawa State has an extremely high maternal mortality ratio underscoring the urgent need for health systems improvement and interventions to accelerate reductions in MMR. The trial is registered at clinicaltrials.gov ( NCT01487707 ). Initially registered on December 6, 2011.

Causes of adult female deaths in Bangladesh: findings from two National Surveys.

PubMed

Nahar, Quamrun; El Arifeen, Shams; Jamil, Kanta; Streatfield, Peter Kim

2015-09-18

Assessment of causes of death and changes in pattern of causes of death over time are needed for programmatic purposes. Limited national level data exist on the adult female causes of death in Bangladesh. Using data from two nationally representation surveys, the 2001 and 2010 Bangladesh Maternal Mortality Surveys (BMMS), the paper examines the causes of adult female death, aged 15-49 years, and changes in the patterns of these deaths. In both surveys, all household deaths three years prior to the survey were identified. Adult female deaths were then followed by a verbal autopsy (VA) using the WHO structured questionnaire. Two physicians independently reviewed the VA forms to assign a cause of death using the ICD-10; in case of disagreement, a third physician made an independent review and assigned a cause of death. The overall mortality rates for women aged 15-49 in 2001 and 2010 were 182 per 100,000 and 120 per 100,000 respectively. There is a shift in the pattern of causes of death during the period covered by the two surveys. In the 2001 survey, the main causes of death were maternal (20 %), followed by diseases of the circulatory system (15 %), malignancy (14 %) and infectious diseases (13 %). However, in the 2010 survey, malignancies were the leading cause (21 %), followed by diseases of the circulatory system (16 %), maternal causes (14 %) and infectious diseases (8 %). While maternal deaths remained the number one cause of death among 20-34 years old in both surveys, unnatural deaths were the main cause for teenage deaths, and malignancies were the main cause of death for older women. Although there is an increasing trend in the proportion of women who died in hospitals, in both surveys most women died at home (74 % in 2001 and 62 % in 2010). The shift in the pattern of causes of adult female deaths is in agreement with the overall change in the disease pattern from communicable to non-communicable diseases in Bangladesh. Suicide and other violent deaths as the primary cause of deaths among teenage girls demands specific interventions to prevent such premature deaths. Prevention of deaths due to non-communicable diseases should also be a priority.

Classification of stillbirths is an ongoing dilemma.

PubMed

Nappi, Luigi; Trezza, Federica; Bufo, Pantaleo; Riezzo, Irene; Turillazzi, Emanuela; Borghi, Chiara; Bonaccorsi, Gloria; Scutiero, Gennaro; Fineschi, Vittorio; Greco, Pantaleo

2016-10-01

To compare different classification systems in a cohort of stillbirths undergoing a comprehensive workup; to establish whether a particular classification system is most suitable and useful in determining cause of death, purporting the lowest percentage of unexplained death. Cases of stillbirth at gestational age 22-41 weeks occurring at the Department of Gynecology and Obstetrics of Foggia University during a 4 year period were collected. The World Health Organization (WHO) diagnosis of stillbirth was used. All the data collection was based on the recommendations of an Italian diagnostic workup for stillbirth. Two expert obstetricians reviewed all cases and classified causes according to five classification systems. Relevant Condition at Death (ReCoDe) and Causes Of Death and Associated Conditions (CODAC) classification systems performed best in retaining information. The ReCoDe system provided the lowest rate of unexplained stillbirth (14%) compared to de Galan-Roosen (16%), CODAC (16%), Tulip (18%), Wigglesworth (62%). Classification of stillbirth is influenced by the multiplicity of possible causes and factors related to fetal death. Fetal autopsy, placental histology and cytogenetic analysis are strongly recommended to have a complete diagnostic evaluation. Commonly employed classification systems performed differently in our experience, the most satisfactory being the ReCoDe. Given the rate of "unexplained" cases, none can be considered optimal and further efforts are necessary to work out a clinically useful system.

Assessment of the reliability of data collected for the Department of Veterans Affairs national surgical quality improvement program.

PubMed

Davis, Chester L; Pierce, John R; Henderson, William; Spencer, C David; Tyler, Christine; Langberg, Robert; Swafford, Jennan; Felan, Gladys S; Kearns, Martha A; Booker, Brigitte

2007-04-01

The Office of the Medical Inspector of the Department of Veterans Affairs (VA) studied the reliability of data collected by the VA's National Surgical Quality Improvement Program (NSQIP). The study focused on case selection bias, accuracy of reports on patients who died, and interrater reliability measurements of patient risk variables and outcomes. Surgical data from a sample of 15 VA medical centers were analyzed. For case selection bias, reviewers applied NSQIP criteria to include or exclude 2,460 patients from the database, comparing their results with those of NSQIP staff. For accurate reporting of patients who died, reviewers compared Social Security numbers of 10,444 NSQIP records with those found in the VA Beneficiary Identification and Records Locator Subsystem, VA Patient Treatment Files, and Social Security Administration death files. For measurement of interrater reliability, reviewers reabstracted 59 variables in each of 550 patient medical records that also were recorded in the NSQIP database. On case selection bias, the reviewers agreed with NSQIP decisions on 2,418 (98%) of the 2,460 cases. Computer record matching identified 4 more deaths than the NSQIP total of 198, a difference of about 2%. For 52 of the categorical variables, agreement, uncorrected for chance, was 96%. For 48 of 52 categorical variables, kappas ranged from 0.61 to 1.0 (substantial to almost perfect agreement); none of the variables had kappas of less than 0.20 (slight to poor agreement). This sample of medical centers shows adherence to criteria in selecting cases for the NSQIP database, for reporting deaths, and for collecting patient risk variables.

Life-after-death beliefs and self motivations.

PubMed

Echebarría Echabe, Agustin; Perez, Saioa

2017-01-01

An experimental study was designed to ascertain whether three self-motives (death-thoughts avoidance, self-uncertainty reduction, and need-for-control) are irreducible motives or examples of a more basic primary motive with regard to their relationship to life-after-death (LAD) beliefs. The study explored the impact of the three self-motives on adherence to LAD beliefs through three mediators: self-esteem, feelings of disquiet, and thoughts-accessibility (thoughts of death, need-for-control, and uncertainty). Participants were randomly assigned to write about their own death, a time they felt uncertain, a time they felt powerless, or about a toothache episode. The mediators (accessibility of disturbing thoughts, feelings of disquiet-uncertainty, and self-esteem) were measured next. The dependent variable selected was endorsement of LAD beliefs. Results showed that the cognitive and emotional responses produced by the activation of the three motives were similar. The three motives increased the accessibility of uncertain-related thoughts that, in turn, increased the adherence to LAD.

The ethics of limiting informed debate: censorship of select medical publications in the interest of organ transplantation.

PubMed

Potts, Michael; Verheijde, Joseph L; Rady, Mohamed Y; Evans, David W

2013-12-01

Recently, several articles in the scholarly literature on medical ethics proclaim the need for "responsible scholarship" in the debate over the proper criteria for death, in which "responsible scholarship" is defined in terms of support for current neurological criteria for death. In a recent article, James M. DuBois is concerned that academic critiques of current death criteria create unnecessary doubt about the moral acceptability of organ donation, which may affect the public's willingness to donate. Thus he calls for a closing of the debate on current death criteria and for journal editors to publish only critiques that "substantially engage and advance the debate." We argue that such positions as DuBois' are a threat to responsible scholarship in medical ethics, especially scholarship that opposes popular stances, because it erodes academic freedom and the necessity of debate on an issue that is literally a matter of life and death, no matter what side a person defends.

Paleodemographic age-at-death distributions of two Mexican skeletal collections: a comparison of transition analysis and traditional aging methods.

PubMed

Bullock, Meggan; Márquez, Lourdes; Hernández, Patricia; Ruíz, Fernando

2013-09-01

Traditional methods of aging adult skeletons suffer from the problem of age mimicry of the reference collection, as described by Bocquet-Appel and Masset (1982). Transition analysis (Boldsen et al., 2002) is a method of aging adult skeletons that addresses the problem of age mimicry of the reference collection by allowing users to select an appropriate prior probability. In order to evaluate whether transition analysis results in significantly different age estimates for adults, the method was applied to skeletal collections from Postclassic Cholula and Contact-Period Xochimilco. The resulting age-at-death distributions were then compared with age-at-death distributions for the two populations constructed using traditional aging methods. Although the traditional aging methods result in age-at-death distributions with high young adult mortality and few individuals living past the age of 50, the age-at-death distributions constructed using transition analysis indicate that most individuals who lived into adulthood lived past the age of 50. Copyright © 2013 Wiley Periodicals, Inc.

Autophagy and Apoptosis Act as Partners to Induce Germ Cell Death after Heat Stress in Mice

PubMed Central

Zhang, Mianqiu; Jiang, Min; Bi, Ye; Zhu, Hui; Zhou, Zuomin; Sha, Jiahao

2012-01-01

Testicular heating suppresses spermatogenesis which is marked by germ cell loss via apoptotic pathways. Recently, it is reported that autophagy also can be induced by heat treatment in somatic cells. In this study, the status of autophagy in germ cells after heat treatment, as well as the partnership between autophagy and apoptosis in these cells was investigated. The results demonstrated that besides initiating apoptotic pathways, heat also induced autophagic pathways in germ cells. Exposure of germ cells to hyperthermia resulted in several specific features of the autophagic process, including autophagosome formation and the conversion of LC3-I to LC3-II. Furthermore, the ubiquitin-like protein conjugation system was implicated as being likely responsible for heat-induced autophagy in germ cells since all genes involving this system were found to be expressed in the testes. In addition, the upstream protein in this system, Atg7 (Autophagy-related gene 7), was found to be expressed in all types of spermatogenic cells, and its expression level was positively correlated with the level of autophagy in germ cells. As a result, Atg7 was selected as the investigative target to further analyze the role of autophagy in heat-induced germ cell death. It was shown that down expression of Atg7 protein resulted in the notable decrease in the level of autophagy in heat-treated germ cells, and this down-regulation of autophagy caused by Atg7 knockdown further reduced the apoptotic rate of germ cells. These results suggest that autophagy plays a positive role in the process of germ cell apoptosis after heat treatment. In conclusion, this study demonstrates that heat triggers autophagy and apoptosis in germ cells. These two mechanisms might act as partners, not antagonist, to induce cell death and lead to eventual destruction of spermatogenesis. PMID:22848486

Use of verbal autopsy and social autopsy in humanitarian crises

PubMed Central

Balabanova, Dina

2018-01-01

Introduction Two billion people live in countries affected by conflict, violence and fragility. These are exceptional situations in which mortality shifts dramatically and in which civil registration and vital statistics systems are often weakened or cease to function. Verbal autopsy and social autopsy (VA and SA) are methods used to assign causes of death and understand the contexts in which these occur, in settings where information is otherwise unavailable. This review sought to explore the use of VA and SA in humanitarian crises, with a focus on how these approaches are used to inform policy and programme responses. Methods A rapid scoping review was conducted on the use of VA and SA in humanitarian crises in low and middle-income countries since 1991. Drawing on a maximum variation approach, two settings of application (‘application contexts’) were selected and investigated via nine semi-structured expert interviews. Results VA can determine causes of death in crisis-affected populations where no other registration system is in place. Combined with SA and active community involvement, these methods can deliver a holistic view of obstacles to seeking and receiving essential healthcare, yielding context-specific information to inform appropriate responses. The contexts in which VA and SA are used require adaptations to standard tools, and new mobile developments in VA raise specific ethical considerations. Furthermore, collecting and sythesising data in a timely, continuous manner, and ensuring coordination and communication between agencies, is important to realise the potential of these approaches. Conclusion VA and SA are valuable research methods to foster evidence-informed responses for populations affected by humanitarian crises. When coordinated and communicated effectively, data generated through these methods can help to identify levels, causes and circumstances of deaths among vulnerable groups, and can enable planning and allocating resources effectively, potentially improving health system resilience to future crises. PMID:29736275

Practicing Surgeons Lead in Quality Care, Safety, and Cost Control

PubMed Central

Shively, Eugene H.; Heine, Michael J.; Schell, Robert H.; Sharpe, J Neal; Garrison, R Neal; Vallance, Steven R.; DeSimone, Kenneth J.S.; Polk, Hiram C.

2004-01-01

Objective: To report the experiences of 66 surgical specialists from 15 different hospitals who performed 43 CPT-based procedures more than 16,000 times. Summary Background Data: Surgeons are under increasing pressure to demonstrate patient safety data as quantitated by objective and subjective outcomes that meet or exceed the standards of benchmark institutions or databases. Methods: Data from 66 surgical specialists on 43 CPT-based procedures were accessioned over a 4-year period. The hospitals vary from a small 30-bed hospital to large teaching hospitals. All reported deaths and complications were verified from hospital and office records and compared with benchmarks. Results: Over a 4-year inclusive period (1999–2002), 16,028 elective operations were accessioned. There was a total 1.4% complication rate and 0.05% death rate. A system has been developed for tracking outcomes. A wide range of improvements have been identified. These include the following: 1) improved classification of indications for systemic prophylactic antibiotic use and reduction in the variety of drugs used, 2) shortened length of stay for standard procedures in different surgical specialties, 3) adherence to strict indicators for selected operative procedures, 4) less use of costly diagnostic procedures, 5) decreased use of expensive home health services, 6) decreased use of very expensive drugs, 7) identification of the unnecessary expense of disposable laparoscopic devices, 8) development of a method to compare a one-surgeon hospital with his peers, and 9) development of unique protocols for interaction of anesthesia and surgery. The system also provides a very good basis for confirmation of patient safety and improvement therein. Conclusions: Since 1998, Quality Surgical Solutions, PLLC, has developed simple physician-authored protocols for delivering high-quality and cost-effective surgery that measure up to benchmark institutions. We have discovered wide areas for improvements in surgery by adherence to simple protocols, minimizing death and complications and clarifying cost issues. PMID:15166954

Classification systems for causes of stillbirth and neonatal death, 2009-2014: an assessment of alignment with characteristics for an effective global system.

PubMed

Leisher, Susannah Hopkins; Teoh, Zheyi; Reinebrant, Hanna; Allanson, Emma; Blencowe, Hannah; Erwich, Jan Jaap; Frøen, J Frederik; Gardosi, Jason; Gordijn, Sanne; Gülmezoglu, A Metin; Heazell, Alexander E P; Korteweg, Fleurisca; Lawn, Joy; McClure, Elizabeth M; Pattinson, Robert; Smith, Gordon C S; Tunçalp, Ӧzge; Wojcieszek, Aleena M; Flenady, Vicki

2016-09-15

To reduce the burden of 5.3 million stillbirths and neonatal deaths annually, an understanding of causes of deaths is critical. A systematic review identified 81 systems for classification of causes of stillbirth (SB) and neonatal death (NND) between 2009 and 2014. The large number of systems hampers efforts to understand and prevent these deaths. This study aimed to assess the alignment of current classification systems with expert-identified characteristics for a globally effective classification system. Eighty-one classification systems were assessed for alignment with 17 characteristics previously identified through expert consensus as necessary for an effective global system. Data were extracted independently by two authors. Systems were assessed against each characteristic and weighted and unweighted scores assigned to each. Subgroup analyses were undertaken by system use, setting, type of death included and type of characteristic. None of the 81 systems were aligned with more than 9 of the 17 characteristics; most (82 %) were aligned with four or fewer. On average, systems were aligned with 19 % of characteristics. The most aligned system (Frøen 2009-Codac) still had an unweighted score of only 9/17. Alignment with individual characteristics ranged from 0 to 49 %. Alignment was somewhat higher for widely used as compared to less used systems (22 % v 17 %), systems used only in high income countries as compared to only in low and middle income countries (20 % vs 16 %), and systems including both SB and NND (23 %) as compared to NND-only (15 %) and SB-only systems (13 %). Alignment was higher with characteristics assessing structure (23 %) than function (15 %). There is an unmet need for a system exhibiting all the characteristics of a globally effective system as defined by experts in the use of systems, as none of the 81 contemporary classification systems assessed was highly aligned with these characteristics. A particular concern in terms of global effectiveness is the lack of alignment with "ease of use" among all systems, including even the most-aligned. A system which meets the needs of users would have the potential to become the first truly globally effective classification system.

22 CFR 19.11-6 - Death during active duty.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Death during active duty. 19.11-6 Section 19.11... PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.11-6 Death during active duty. (a...-2 computed as if the participant had retired on the date of death unless a court order or spousal...

5 CFR 847.211 - Death of employee during election opportunity period.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Death of employee during election... Qualifying Move § 847.211 Death of employee during election opportunity period. (a) When an employee eligible... employee is deemed to have made the election and to be covered, at time of death, by the retirement system...

22 CFR 19.11-6 - Death during active duty.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Death during active duty. 19.11-6 Section 19.11... PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.11-6 Death during active duty. (a...-2 computed as if the participant had retired on the date of death unless a court order or spousal...

22 CFR 19.11-6 - Death during active duty.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Death during active duty. 19.11-6 Section 19.11... PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.11-6 Death during active duty. (a...-2 computed as if the participant had retired on the date of death unless a court order or spousal...

5 CFR 847.211 - Death of employee during election opportunity period.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Death of employee during election... Qualifying Move § 847.211 Death of employee during election opportunity period. (a) When an employee eligible... employee is deemed to have made the election and to be covered, at time of death, by the retirement system...

22 CFR 19.11-6 - Death during active duty.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Death during active duty. 19.11-6 Section 19.11... PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.11-6 Death during active duty. (a...-2 computed as if the participant had retired on the date of death unless a court order or spousal...