944 resultados para serious
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The aim of this study was to validate a multiplex PCR for the species identification and serotyping of Actinobacillus pleuropneumoniae serovars 1, 5, 7, 12 and 15. All 15 reference strains and 411 field isolates (394 from Australia, 11 from Indonesia, five from Mexico and one from New Zealand) of A. pleuropneumoniae were tested with the multiplex PCR. The specificity of this multiplex PCR was validated on 26 non-A. pleuropneumoniae species. The multiplex PCR gave the expected results with all 15 serovar reference strains and agreed with conventional serotyping for all field isolates from serovars 1 (n = 46), 5 (n = 81), 7 (n = 80), 12 (n = 16) and serovar 15 (n = 117). In addition, a species-specific product was amplified in the multiplex PCR with all 411 A. pleuropneumoniae field isolates. Of 25 nontypeable field isolates only two did not yield a serovar-specific band in the multiplex PCR. This multiplex PCR for serovars 1, 5, 7, 12 and 15 is species specific and capable of serotyping isolates from diverse locations. Significance and Impact of the Study A multiplex PCR that can recognize serovars 1, 5, 7, 12 and 15 of A. pleuropneumoniae was developed and validated. This novel diagnostic tool will enable frontline laboratories to provide key information (the serovar) to guide targeted prevention and control programmes for porcine pleuropneumonia, a serious economic disease of pigs. The previous technology, traditional serotyping, is typically provided by specialized reference laboratories, limiting the capacity to respond to this key disease.
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A recent controversy in the United States over drug pricing by Turing Pharmaceuticals AG has raised larger issues in respect of intellectual property, access to medicines, and the Trans-Pacific Partnership (TPP). In August 2015, Turing Pharmaceuticals AG – a private biopharmaceutical company with offices in New York, the United States, and Zug, Switzerland - acquired the exclusive marketing rights to Daraprim in the United States from Impax Laboratories Incorporated. Martin Shkreli, Turing’s Founder and Chief Executive Officer, maintained: “The acquisition of Daraprim and our toxoplasmosis research program are significant steps along Turing’s path of bringing novel medications to patients with serious disorders, some of whom often go undiagnosed and untreated.” He emphasised: “We intend to invest in the development of new drug candidates that we hope will yield an even better clinical profile, and also plan to launch an educational effort to help raise awareness and improve diagnosis for patients with toxoplasmosis.” In September 2015, there was much public controversy over the decision of Martin Shkreli to raise the price of a 62 year old drug, Daraprim, from $US13.50 to $US750 a pill. The drug is particularly useful in respect to the treatment and prevention of malaria, and in the treatment of infections in individuals with HIV/AIDS. Daraprim is listed on the World Health Organization’s (WHO) List of Essential Medicines. In the face of much criticism, Martin Shkreli has said that he will reduce the price of Daraprim. He observed: “We've agreed to lower the price on Daraprim to a point that is more affordable and is able to allow the company to make a profit, but a very small profit.” He maintained: “We think these changes will be welcomed.” However, he has been vague and ambiguous about the nature of the commitment. Notably, the lobby group, Pharmaceutical Research and Manufacturers of America (PhARMA), disassociated itself from the claims of Turing Pharmaceuticals. The group said: “PhRMA members have a long history of drug discovery and innovation that has led to increased longevity and improved lives for millions of patients.” The group noted: “Turing Pharmaceutical is not a member of PhRMA and we do not embrace either their recent actions or the conduct of their CEO.” The biotechnology peak body Biotechnology Industry Organization also sought to distance itself from Turing Pharmaceuticals. A hot topic: United States political debate about access to affordable medicines This controversy over Daraprim is unusual – given the age of drug concerned. Daraprim is not subject to patent protection. Nonetheless, there remains a monopoly in respect of the marketplace. Drug pricing is not an isolated problem. There have been many concerns about drug pricing – particularly in respect of essential medicines for HIV/AIDS, tuberculosis, and malaria. This recent controversy is part of a larger debate about access to affordable medicines. The dispute raises larger issues about healthcare, consumer rights, competition policy, and trade. The Daraprim controversy has provided impetus for law reform in the US. US Presidential Candidate Hillary Clinton commented: “Price gouging like this in this specialty drug market is outrageous.” In response to her comments, the Nasdaq Biotechnology Index fell sharply. Hillary Clinton has announced a prescription drug reform plan to protect consumers and promote innovation – while putting an end to profiteering. On her campaign site, she has emphasised that “affordable healthcare is a basic human right.” Her rival progressive candidate, Bernie Sanders, was also concerned about the price hike. He wrote a letter to Martin Shkreli, complaining about the price increase for the drug Daraprim. Sanders said: “The enormous, overnight price increase for Daraprim is just the latest in a long list of skyrocketing price increases for certain critical medications.” He has pushed for reforms to intellectual property to make medicines affordable. The TPP and intellectual property The Daraprim controversy and political debate raises further issues about the design of the TPP. The dispute highlights the dangers of extending the rights of pharmaceutical drug companies under intellectual property, investor-state dispute settlement, and drug administration. Recently, the civil society group Knowledge Ecology International published a leaked draft of the Intellectual Property Chapter of the TPP. Knowledge Ecology International Director, James Love, was concerned the text revealed that the US “continues to be the most aggressive supporter of expanded intellectual property rights for drug companies.” He was concerned that “the proposals contained in the TPP will harm consumers and in some cases block innovation.” James Love feared: “In countless ways, the Obama Administration has sought to expand and extend drug monopolies and raise drug prices.” He maintained: “The astonishing collection of proposals pandering to big drug companies make more difficult the task of ensuring access to drugs for the treatment of cancer and other diseases and conditions.” Love called for a different approach to intellectual property and trade: “Rather than focusing on more intellectual property rights for drug companies, and a death-inducing spiral of higher prices and access barriers, the trade agreement could seek new norms to expand the funding of medical research and development (R&D) as a public good, an area where the US has an admirable track record, such as the public funding of research at the National Institutes of Health (NIH) and other federal agencies.” In addition, there has been much concern about the Investment Chapter of the TPP. The investor-state dispute settlement regime would enable foreign investors to challenge government policy making, which affected their investments. In the context of healthcare, there is a worry that pharmaceutical drug companies will deploy their investor rights to challenge public health measures – such as, for instance, initiatives to curb drug pricing and profiteering. Such concerns are not merely theoretical. Eli Lilly has brought an investor action against the Canadian Government over the rejection of its drug patents under the investor-state dispute settlement regime of the North American Free Trade Agreement (NAFTA). The Health Annex to the TPP also raises worries that pharmaceutical drug companies will able to object to regulatory procedures in respect of healthcare. It is disappointing that the TPP – in the leaks that we have seen – has only limited recognition of the importance of access to essential medicines. There is a need to ensure that there are proper safeguards to provide access to essential medicines – particularly in respect of HIV/AIDs, malaria, and tuberculosis. Moreover, there must be protection against drug profiteering and price gouging in any trade agreement. There should be strong measures against the abuse of intellectual property rights. The dispute over Turing Pharmaceuticals AG and Daraprim is an important cautionary warning in respect of some of the dangers present in the secret negotiations in respect of the TPP. There is a need to preserve consumer rights, competition policy, and public health in trade negotiations over an agreement covering the Pacific Rim.
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This review focuses on key trends in resistance to chemical treatments in stored product pests, and advances in resistance management, with an emphasis on resistance to the fumigant phosphine. Findings: Phosphine resistance continues to be a major concern. In particular, phosphine resistance in Cryptolestes ferrugineus has emerged as a serious issue, with some populations exhibiting the strongest level detected so far for this fumigant. In response, a 'quick knock down test' has been established to deliver industry and scientists 'same day' advice on the resistance status of field samples; sulfuryl fluoride is being developed as a 'resistance breaker' and phosphine dosages are being revised to manage this problem. There has been major progress in identifying the genes responsible for phosphine resistance and the development of molecular resistance diagnostics for key pests. Several studies on Rhyzopertha dominica have demonstrated that molecular screening can be used to determine the frequency of resistance alleles in samples collected from farm storages. Despite on-going research in several pests, there is no definitive answer to the question of whether there is a fitness cost associated phosphine resistance, with some studies showing a clear cost and others none. Evidence continues to emerge of resistance to grain protectants, including the juvenile hormone analogue methoprene. The development and adoption of spinosad, as a next generation 'green' treatment, and the use of protectant combinations provides opportunities to counter the problem of protectant resistance.Directions for future research: A uniform set of protocols should be developed for phosphine resistance detection for all major species. It should combine 'quick tests' and molecular diagnostics to be adopted internationally. Research is required on the establishment of a decision making system that integrates newly developed grain protectants and fumigants, other alternative control methods, as well as an accurate and rapid resistance detection system for early warning of the emergence of new resistances.
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Purpose To evaluate if adding clonidine to a standard nerve root block containing local anaesthetic and steroid improved the outcome of patients with severe lumbar nerve root pain secondary to MRI proven lumbar disc prolapse. Methods We undertook a single blind, prospective, randomised controlled trial evaluating 100 consecutive patients with nerve root pain secondary to lumbar disc prolapse undergoing trans-foraminal epidural steroid injection either with or without the addition of clonidine. 50 patients were allocated to each arm of the study. The primary outcome measure was the avoidance of a second procedure- repeat injection or micro-discectomy surgery. Secondary outcome measures were also studied: pain scores for leg and back pain using a visual analogue scale (VAS), the Roland Morris Disability Questionnaire (RMDQ) and the Measure Your Own Medical Outcome Profile (MYMOP). Follow up was carried out at 6 weeks, 6 months and 1 year. Results No serious complications occurred. Of the 50 patients who received the addition of clonidine, 56% were classified as successful injections, with no further intervention required, as opposed to 40% who received the standard injection. This difference did not reach statistical significance (p=0.109, chi-squared test). All secondary measures showed no statistically significant differences between the groups except curiously, the standard group who had been classified as successful had better leg pain relief than the clonidine group (p=0.026) at 1 year. Conclusions This pilot study has shown a 16% treatment effect with adding clonidine to lumbar nerve root blocks and that it is a safe injectate for this purpose.
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Usability testing is a productive and reliable method for evaluating the usability of software. Planning and implementing the test and analyzing its results is typically considered time-consuming, whereas applying usability methods in general is considered difficult. Because of this, usability testing is often priorized lower than more concrete issues in software engineering projects. Intranet Alma is a web service, users of which consist of students and personnel of the University of Helsinki. Alma was published in 2004 at the opening ceremony of the university. It has 45 000 users, and it replaces several former university network services. In this thesis, the usability of intranet Alma is evaluated with usability testing. The testing method applied has been lightened to make its taking into use as easy as possible. In the test, six students each tried to solve nine test tasks with Alma. As a result concrete usability problems were described in the final test report. Goal-orientation was given less importance in the applied usability testing. In addition, the system was tested only with test users from the largest user group. Usability test found general usability problems that occurred no matter the task or the user. However, further evaluation needs to be done: in addition to the general usability problems, there are task-dependent problems, solving of which requires thorough gathering of users goals. In the basic structure and central functionality of Alma, for example in navigation, there are serious and often repeating usability problems. It would be of interest to verify the designed user interface solutions to these problems before taking them into use. In the long run, the goals of the users, that the software is planned to support, are worth gathering, and the software development should be based on these goals.
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The vastly increased popularity of the Internet as an effective publication and distribution channel of digital works has created serious challenges to enforcing intellectual property rights. Works are widely disseminated on the Internet, with and without permission. This thesis examines the current problems with licence management and copy protection and outlines a new method and system that solve these problems. The WARP system (Works, Authors, Royalties, and Payments) is based on global registration and transfer monitoring of digital works, and accounting and collection of Internet levy funded usage fees payable to the authors and right holders of the works. The detection and counting of downloads is implemented with origrams, short and original parts picked from the contents of the digital work. The origrams are used to create digests, digital fingerprints that identify the piece of work transmitted over the Internet without the need to embed ID tags or any other easily removable metadata in the file.
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Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm(3)g(-1)) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 mu g)/SV-140 (500 mu g) and FD oE2 (100 mu g)/SV-140 (500 mu g) to induce long-term immunity was compared to immunisation with oE2 (100 mu g) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 mu g) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 mu g SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications.
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Screwworms are obligate, invasive parasites of warm-blooded animals. The female flies lay batches of eggs at the edge of wounds or other lesions. These eggs hatch to larvae or screw-worms which feed on affected animals for 6-7 days, burrowing deeply into subcutaneous tissues and causing severe trauma to animals, production loss and potentially death. Susceptible sites include wounds resulting from management practices such as castration, de-horning and ear tagging and lesions caused by the activities of other parasites such as buffalo flies and ticks. The navels of the new born and the vulval region of their mothers following parturition are highly susceptible and body orifices such as nose and ears are also frequent targets for ovipositing screwworm flies. The Old World screw-worm, Chrysomya bezziana (OWS) is considered one of the most serious exotic insect pest threatening Australia's livestock industries and is endemic in a number of our closest neighbouring countries. New World screwworm (NWS), Cochliomyia hominivorax, endemic to South America, has also entered Australia on at least 2 occasions. Many tropical and subtropical areas of Australia are suitable for the establishment of OWS and the potential range is expected to increase with climate change. The Australian screwworm preparedness strategy indicates a program of containment with chemical treatments followed by eradication of OWS using sterile male release and parasiticides. However, there is no longer an operational OWS sterile insect screw-worm facility anywhere in the world and establishing a large scale production facility would most optimistically take at least 2 years. In the interim, containment would be almost totally dependent on the availability of effective chemical controls. A review of chemical formulations available for potential use against OWS in Australia found that currently only one chemical, ivermectin administered by subcutaneous injection (s.c.) is registered for use against OWS and that many of the chemicals previously shown to be effective against OWS were no longer registered for animal use in Australia.18 From this review a number of Australian-registered chemicals were recommended as a priority for testing against OWS. The Australian Pesticides and Veterinary Medicines Authority (APVMA) can issue an emergency use permit for use of pesticides if they are registered in Australia for other animal uses and shown to be effective against OWS. This project tested the therapeutic and prophylactic efficacy of chemicals with potential for use in the treatment and control of OWS.
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Sown pasture rundown and declining soil fertility for forage crops are too serious to ignore with losses in beef production of up to 50% across Queensland. The feasibility of using strategic applications of nitrogen (N) fertiliser to address these losses was assessed by analysing a series of scenarios using data drawn from published studies, local fertiliser trials and expert opinion. While N fertilser can dramatically increase productivity (growth, feed quality and beef production gains of over 200% in some scenarios), the estimated economic benefits, derived from paddock level enterprise budgets for a fattening operation, were much more modest. In the best-performing sown grass scenarios, average gross margins were doubled or tripled at the assumed fertiliser response rates, and internal rates of return of up to 11% were achieved. Using fertiliser on forage sorghum or oats was a much less attractive option and, under the paddock level analysis and assumptions used, forages struggled to be profitable even on fertile sites with no fertiliser input. The economics of nitrogen fertilising on grass pasture were sensitive to the assumed response rates in both pasture growth and liveweight gain. Consequently, targeted research is proposed to re-assess the responses used in this analysis, which are largely based on research 25-40 years ago when soils were generally more fertile and pastures less rundown.
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The lesser auger beetle, Heterobostrychus aequalis (Waterhouse), is a serious pest of seasoned hardwood timber throughout the Oriental region and several areas beyond. Some early collection records of H. aequalis from Australia in the 1950s and 1960s indicated that the insect was present in northern Queensland, but no confirmed breeding population has been found in the past few decades suggesting either that it may have not established permanently or it is difficult to detect. The ambiguity about the breeding status of the pest in Australia has caused confusion for regulating authorities needing to respond to each new post-border detection. We examined records of H. aequalis in Australian insect collections and from intensive plant pest surveillance activities in Queensland and northern Australia over the past 48 years to resolve this confusion. Until very recently, available evidence suggested that H. aequalis was not established in Australia, despite multiple introductions and apparently suitable climate and hosts. Collection records of the pest are predominantly linked to intercepted items or are recorded as of unknown origin, and no established populations have been found during many years of targeted surveillance. However, a detection of H. aequalis in suburban Cairns, north Queensland, in late 2013 and two more in mid-2015 in the same general locality do not appear to be linked to any imported material, indicating that there is at least a tenuously established local population. Investigations are underway to confirm this, but the insect is not widely established in Australia and, if present, remains elusive. Our recommended response to any future detection of H. aequalis is to fumigate or destroy the infested material, conduct tracing enquiries and limit surveys to the immediate vicinity of the detection.
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Background Malnutrition and unintentional weight loss are major clinical issues in people with dementia living in residential aged care facilities (RACFs) and are associated with serious adverse outcomes. However, evidence regarding effective interventions is limited and strategies to improve the nutritional status of this population are required. This presentation describes the implementation and results of a pilot randomised controlled trial of a multi-component intervention for improving the nutritional status of RACF residents with dementia. Method Fifteen residents with moderate-severe dementia living in a secure long-term RACF participated in a five week pilot study. Participants were randomly allocated to either an Intervention (n=8) or Control group (n=7). The intervention comprised four elements delivered in a separate dining room at lunch and dinner: the systematic reinforcement of residents’ eating behaviors using a specific communication protocol; family-style dining; high ambiance table presentation; and routine Dietary-Nutrition Champion supervision. Control group participants ate their meals according to the facility’s standard practice. Baseline and follow-up assessments of nutritional status, food consumption, and body mass index were obtained by qualified nutritionists. Additional assessments included measures of cognitive functioning, mealtime agitation, depression, wandering status and multiple measures of intervention fidelity. Results No participant was malnourished at study commencement and participants in both groups gained weight from follow-up to baseline which was not significantly different between groups (t=0.43; p=0.67). A high degree of treatment fidelity was evident throughout the intervention. Qualitative data from staff indicate the intervention was perceived to be beneficial for residents. Conclusions This multi-component nutritional intervention was well received and was feasible in the RACF setting. Participants’ sound nutritional status at baseline likely accounts for the lack of an intervention effect. Further research using this protocol in malnourished residents is recommended. For success, a collaborative approach between researchers and facility staff, particularly dietary staff, is essential.
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A5-GMR-1 is a synchronous stream cipher used to provide confidentiality for communications between satellite phones and satellites. The keystream generator may be considered as a finite state machine, with an internal state of 81 bits. The design is based on four linear feedback shift registers, three of which are irregularly clocked. The keystream generator takes a 64-bit secret key and 19-bit frame number as inputs, and produces an output keystream of length between $2^8$ and $2^{10}$ bits. Analysis of the initialisation process for the keystream generator reveals serious flaws which significantly reduce the number of distinct keystreams that the generator can produce. Multiple (key, frame number) pairs produce the same keystream, and the relationship between the various pairs is easy to determine. Additionally, many of the keystream sequences produced are phase shifted versions of each other, for very small phase shifts. These features increase the effectiveness of generic time-memory tradeoff attacks on the cipher, making such attacks feasible.
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Eight Cylindropuntia species have naturalised in Australia and pose serious economic, environmental and social impacts. Two biotypes of Dactylopius tomentosus have been used as bio-control agents to control different Cylindropuntia species. The host range of four additional biotypes of Dactylopius tomentosus from southern USA was investigated. Feeding and development were restricted to the genus Cylindropuntia. However, they showed differences in specificity within this genus and some biotypes discriminated between the provenances of C. rosea and C. tunicata. Efficacy trials were conducted to determine whether populations of each biotype could be sustained on the naturalised Cylindropuntia species and if these populations could retard the growth or kill these plants. The acanthocarpa biotype offers potential control of C. rosea (Lorne Station), while the cylindropuntia sp. biotype shows great potential to control C. rosea (Grawin). The cylindropuntia sp. biotype also had a high impact on C. kleiniae and C. imbricata, and a moderate impact on C. leptocaulis and C. prolifera. The acanthocarpa X echinocarpa biotype had its greatest impact on C. tunicata (Grawin), killing this plant in 18 weeks. A fourth biotype, leptocaulis, was damaging to some species, but was less effective than the other biotypes. Cylindropuntia spinosior is the only naturalised species in Australia where no effective biocontrol agent has been found.
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Chlamydia trachomatis infections can result in the development of serious sequelae such as pelvic inflammatory disease and tubal infertility. In this study, peripheral blood mononuclear cells from women who were undergoing or had recently undergone IVF treatment were cultured ex vivo with C. trachomatis to identify the immune responses associated with women who had serological evidence of a history of Chlamydia infection. Cytokines secreted into the supernatant from the cultures were measured using ELISA, and the level of IL-1β was found to be significantly higher in Chlamydia positive women than Chlamydia negative women. qRT-PCR analysis of the expression of 88 immune-related genes showed trends towards an upregulation of CXCL10, CXCL11 and HLA-A in Chlamydia positive women compared with Chlamydia negative women. These findings support that some women launch a more marked proinflammatory response upon infection with C. trachomatis and this may be associated with why C. trachomatis induces infertility in some infected women.
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The Church in one s heart. The formation of religion and individuation in the lives of Ingrian Finns in the 20th century. Sinikka Haapaniemi University of Helsinki, Finland 302 pages The study falls within the sphere of religious views and the problematique of the life trajectory. The target group comprises those Finnish speakers (Ingrian Finns, Ingrians) living in what was historically Ingermanland and who in varying circumstances became scattered. These times were characterized by pressures for change due to societal reasons and reasons of war. In conditions of change external living conditions matters of religious conviction may assume new meaning and form. The examination focuses on sustaining personal faith in difficult life situations and on how crises affected religious views. Another level of scrutiny takes shape through the terminology of the analytic psychology of C.G. Jung. Individuation is deemed to occur as a cumulative process through the stages of life. The basic data for the study comprises interviews with twenty (20) natives of Ingria and their biographical narratives written in standard language. Many biographical accounts and memoirs serve as secondary data. The interviewees, who were largely selected at random, recounted their lives without questions formulated in advance. The study falls within the field of comparative religion and adheres to the principles of qualitative research practice and the case-study method. Effort was made to get to know each interviewee in the situation which his/her narrative presents. The aim is to pay attention to the interpretations given by the narrators of their various experiences and to understand their meanings on a personal level. The years during which the Ingrians were scattered, wandering and returning raise problems of survival. An individual s own initiative assumes individual forms and emphases. Religion was part of the narrators lives as one factor in the quality of life. Their religious thinking was influenced by both their home upbringing and the teaching of the Church. The interviewees took a serious attitude to the informative teaching of confirmation training. When there was no longer a church, it was claimed that the church travelled with them. Changed circumstances tested the validity of the teachings. The message of the Church institution persisted and helped them to preserve their traditions. A striving for unity and for the presence of a community emerged both in the form of ritual behaviour and in a predilection to sociability. Gradually, as they returned, the activity of the Church of Ingria began to revive. At the turn of the millennium the network of parishes was extensive and cultural activity flourished wherever the Ingrians settled in the postwar decades. Religion is part of the process of individuation. Examination of religion and individuation shows that religion remained an individual view, whose factual base was formed by Christianity and the tradition of the Church. Home upbringing served to orientate, but not to bind. With ageing the importance of independent thought is emphasized, for example in relation to confession, it did not pose a threat to individuality. Keywords: Life story, Religiosity, individuation, Ingrian, the Church of Ingria