| 1. |
- Gremel, Gabriela, et al.
(författare)
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A systematic analysis of commonly used antibodies in cancer diagnostics
- 2014
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 64:2, s. 293-305
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Tidskriftsartikel (refereegranskat)abstract
- AimsImmunohistochemistry plays a pivotal role in cancer differential diagnostics. To identify the primary tumour from a metastasis specimen remains a significant challenge, despite the availability of an increasing number of antibodies. The aim of the present study was to provide evidence-based data on the diagnostic power of antibodies used frequently for clinical differential diagnostics. Methods and resultsA tissue microarray cohort comprising 940 tumour samples, of which 502 were metastatic lesions, representing tumours from 18 different organs and four non-localized cancer types, was analysed using immunohistochemistry with 27 well-established antibodies used in clinical differential diagnostics. Few antibodies, e.g. prostate-specific antigen and thyroglobulin, showed a cancer type-related sensitivity and specificity of more than 95%. A majority of the antibodies showed a low degree of sensitivity and specificity for defined cancer types. Combinations of antibodies provided limited added value for differential diagnostics of cancer types. ConclusionsThe results from analysing 27 diagnostic antibodies on consecutive sections of 940 defined tumours provide a unique repository of data that can empower a more optimal use of clinical immunohistochemistry. Our results highlight the benefit of immunohistochemistry and the unmet need for novel markers to improve differential diagnostics of cancer.
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| 2. |
- Grundmann, Hajo, et al.
(författare)
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A framework for global surveillance of antibiotic resistance
- 2011
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Ingår i: Drug resistance updates. - : Elsevier BV. - 1368-7646 .- 1532-2084. ; 14:2, s. 79-87
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Forskningsöversikt (refereegranskat)abstract
- The foreseen decline in antibiotic effectiveness explains the needs for data to inform the global public health agenda about the magnitude and evolution of antibiotic resistance as a serious threat to human health and development. Opportunistic bacterial pathogens are the cause of the majority of community and hospital-acquired infections worldwide. We provide an inventory of pre-existing regional surveillance programs in the six WHO regions which should form the underpinning for the consolidation of a global network infrastructure and we outline the structural components such as an international network of reference laboratories that need to be put in place to address the void of these crucial data. In addition we suggest to make use of existing Health and Demographic Surveillance Sites (HDSS) to obtain crucial information from communities in resource limited settings at household level in low- and middle-income countries in Asia and Africa. For optimising the use of surveillance data for public health action i.e. priority setting for new drug development, comparative quantification of antibiotic effectiveness at local, national, regional and global level and identification of the action gaps can be helpful.
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| 3. |
- Shrestha, Niraj, et al.
(författare)
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The Host-Encoded Heme Regulated Inhibitor (HRI) Facilitates Virulence-Associated Activities of Bacterial Pathogens
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e68754-
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that cells lacking the heme-regulated inhibitor (HRI) are highly resistant to infection by bacterial pathogens. By examining the infection process in wild-type and HRI null cells, we found that HRI is required for pathogens to execute their virulence-associated cellular activities. Specifically, unlike wild-type cells, HRI null cells infected with the gram-negative bacterial pathogen Yersinia are essentially impervious to the cytoskeleton-damaging effects of the Yop virulence factors. This effect is due to reduced functioning of the Yersinia type 3 secretion (T3S) system which injects virulence factors directly into the host cell cytosol. Reduced T3S activity is also observed in HRI null cells infected with the bacterial pathogen Chlamydia which results in a dramatic reduction in its intracellular proliferation. We go on to show that a HRI-mediated process plays a central role in the cellular infection cycle of the Gram-positive pathogen Listeria. For this pathogen, HRI is required for the post-invasion trafficking of the bacterium to the infected host cytosol. Thus by depriving Listeria of its intracellular niche, there is a highly reduced proliferation of Listeria in HRI null cells. We provide evidence that these infection-associated functions of HRI (an eIF2 alpha kinase) are independent of its activity as a regulator of protein synthesis. This is the first report of a host factor whose absence interferes with the function of T3S secretion and cytosolic access by pathogens and makes HRI an excellent target for inhibitors due to its broad virulence-associated activities.
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| 4. |
- Streatfield, P. Kim, et al.
(författare)
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Adult non-communicable disease mortality in Africa and Asia : evidence from INDEPTH Health and Demographic Surveillance System sites
- 2014
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality.DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates.RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality.CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.
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| 5. |
- Streatfield, P. Kim, et al.
(författare)
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Cause-specific childhood mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Childhood mortality, particularly in the first 5 years of life, is a major global concern and the target of Millennium Development Goal 4. Although the majority of childhood deaths occur in Africa and Asia, these are also the regions where such deaths are least likely to be registered. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.OBJECTIVE: To present a description of cause-specific mortality rates and fractions over the first 15 years of life as documented by INDEPTH Network sites in sub-Saharan Africa and south-east Asia.DESIGN: All childhood deaths at INDEPTH sites are routinely registered and followed up with verbal autopsy (VA) interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provided person-time denominators for mortality rates. Cause-specific mortality rates and cause-specific mortality fractions are presented according to WHO 2012 VA cause groups for neonatal, infant, 1-4 year and 5-14 year age groups.RESULTS: A total of 28,751 childhood deaths were documented during 4,387,824 person-years over 18 sites. Infant mortality ranged from 11 to 78 per 1,000 live births, with under-5 mortality from 15 to 152 per 1,000 live births. Sites in Vietnam and Kenya accounted for the lowest and highest mortality rates reported.CONCLUSIONS: Many children continue to die from relatively preventable causes, particularly in areas with high rates of malaria and HIV/AIDS. Neonatal mortality persists at relatively high, and perhaps sometimes under-documented, rates. External causes of death are a significant childhood problem in some settings.
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| 6. |
- Streatfield, P. Kim, et al.
(författare)
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Cause-specific mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 25362-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Because most deaths in Africa and Asia are not well documented, estimates of mortality are often made using scanty data. The INDEPTH Network works to alleviate this problem by collating detailed individual data from defined Health and Demographic Surveillance sites. By registering all deaths over time and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available.OBJECTIVE: To build a large standardised mortality database from African and Asian sites, detailing the relevant methods, and use it to describe cause-specific mortality patterns.DESIGN: Individual demographic and verbal autopsy (VA) data from 22 INDEPTH sites were collated into a standardised database. The INDEPTH 2013 population was used for standardisation. The WHO 2012 VA standard and the InterVA-4 model were used for assigning cause of death.RESULTS: A total of 111,910 deaths occurring over 12,204,043 person-years (accumulated between 1992 and 2012) were registered across the 22 sites, and for 98,429 of these deaths (88.0%) verbal autopsies were successfully completed. There was considerable variation in all-cause mortality between sites, with most of the differences being accounted for by variations in infectious causes as a proportion of all deaths.CONCLUSIONS: This dataset documents individual deaths across Africa and Asia in a standardised way, and on an unprecedented scale. While INDEPTH sites are not constructed to constitute a representative sample, and VA may not be the ideal method of determining cause of death, nevertheless these findings represent detailed mortality patterns for parts of the world that are severely under-served in terms of measuring mortality. Further papers explore details of mortality patterns among children and specifically for NCDs, external causes, pregnancy-related mortality, malaria, and HIV/AIDS. Comparisons will also be made where possible with other findings on mortality in the same regions. Findings presented here and in accompanying papers support the need for continued work towards much wider implementation of universal civil registration of deaths by cause on a worldwide basis.
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| 7. |
- Streatfield, P Kim, et al.
(författare)
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HIV/AIDS-related mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data.OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia.DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population.RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates.CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.
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| 8. |
- Streatfield, P. Kim, et al.
(författare)
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Malaria mortality in Africa and Asia : evidence from INDEPTH health and demographic surveillance system sites
- 2014
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 7, s. 25369-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies.OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions.DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality.RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level.CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.
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| 9. |
- Streatfield, P Kim, et al.
(författare)
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Mortality from external causes in Africa and Asia : evidence from INDEPTH Health and Demographic Surveillance System Sites
- 2014
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Ingår i: Global Health Action. - : CoAction Publishing. - 1654-9716 .- 1654-9880. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings.OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories.DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates.RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex.CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs.
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