Colonoscopic surveillance in familial colorectal cancer

Colorectal cancer (CRC) is a disease with a high and rising incidence in the industrialized countries. It is the third leading cause of death among cancers in Sweden and the forth worldwide. Important etiological factors are both environmental and lifestyle as well as heritable factors. Familial adenomatous polyposis (FAP) and Lynch syndrome (LS) with known mutations in single high-penetrance genes account for 2-4% of the CRC cases, leaving a large group with familial clustering of CRC without known genetic background. In the majority of cases, CRC seems to be preceded by a benign lesion, the adenoma, which can be detected and removed during a colonoscopy, making prevention feasible. For FAP and LS there are well-established endoscopy prevention programmes, but for the large group with familial clustering these programmes have to be evaluated and risk profiles have to be identified. In an attempt to determine the prevalence of colonic neoplasia in the normal population with average risk for CRC, 745 randomly selected individuals aged 19-70 volunteered for a colonoscopy. One in ten had an adenoma and 2.8% had an advanced lesion but no cancers were discovered. The results may provide a control population for further studies (Paper I). In a European multi-centre study, colonoscopy surveillance in 530 families with familial CRC with a dominant family history of CRC was evaluated. At baseline, 22 (1.4%) prevalent asymptomatic colorectal cancers were diagnosed, 120 (7.6%) individuals had high-risk adenomas and 225 (14.2%) simple adenomas. Interval cancers, more often seen in individuals that have had multiple adenomas, were infrequent, but the incidence of high-risk adenomas and multiple adenomas was high during surveillance. The study resulted in a suggestion of a screening interval of five years, that would be shortened if multiple and/or advanced adenomas occurred (Paper II). The findings at the screening colonoscopy in a population with increased risk of CRC due to family history were compared to the control population in Paper I. The risk population was stratified into four groups: LS, FCRC, TCR and OCR. In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other three risk groups were 14-24% and 4-7%, compared to 10% and 3% in the control group. In three of the four subgroups, the relative risk for adenomas as well as for advanced adenomas was significantly higher than in the control group. Individuals with a family history of colorectal cancer had high prevalence and cumulative risk of adenomas and advanced adenomas, indicating that colonoscopy screening is beneficial in this population (Paper III). In a cohort with an at least twofold increased risk of CRC due to family history, the impact of various family history variables on the prevalence of adenomas and advanced adenomas was assessed. Furthermore, the association between findings at the first colonoscopy and risk of future lesions was studied. The most important risk factors for advanced lesions including cancer at the screening colonoscopy were the number of first-degree relatives and a young family member with CRC. Finding of simple adenomas or hyperplastic polyps at the screening colonoscopy did not seem to predict for subsequent advanced adenomas or cancers (Paper IV)

Lactobacillus reuteri, Infant Allergy Prevention and Childhood Immune Maturation

The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation, resulting in an abnormal postnatal immune maturation. This chapter concerns the theories behind the use of probiotics in randomized prevention trials, and how this supplementation affects the immunity of pregnant women, the immune development in their children, and possibly preventing allergic diseases. Most studies investigating the underlying mechanisms have focused on postnatal microbial exposure. An increasing body of evidence from studies suggests that the maternal microbial environment during pregnancy can program the immune development of the child. In human allergy intervention studies, probiotic supplementation to the mother during pregnancy, as well as to her baby postnatally, may be important for preventive effects. Also, prenatal environmental exposures may alter gene expression via epigenetic mechanisms, aiming to induce physiological adaptations to the anticipated postnatal environment. The maternal microbial environment during pregnancy may program the immune development of the child

Ashcroft v. Iqbal: The Question of a Heightened Standard of Pleading in Qualified Immunity Cases

Background We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at 2 years. The underlying immunological mechanisms are unknown, however. Objective To investigate the immunomodulatory effect of probiotic supplementation on allergen- and mitogen-induced immune responses in children until 2 years of age. Methods Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 children (29 probiotic and 32 placebo treated) and cultured with ovalbumin, birch and cat extract and Phytohaemagglutinin (PHA). Cytokine and chemokine secretion was determined using an in-house multiplexed Luminex assay and ELISA. Real-time PCR was performed to investigate the Ebi3, Foxp3, GATA-3 and T-bet mRNA expression. Results Probiotic treatment was associated with low cat-induced Th2-like responses at 6 months (IL-5, P = 0.01, and IL-13, P = 0.009), with a similar trend for IL-5 at 12 months (P = 0.09). Cat-induced IFN-γ responses were also lower after probiotic than after placebo treatment at 24 months (P = 0.007), with similar findings for the anti-inflammatory IL-10 at birth (P = 0.001) and at 12 months (P = 0.009). At 24 months, Th2-associated CCL22 levels were lower in the probiotic than in the placebo group after birch stimulation (P = 0.02), with a similar trend after ovalbumin stimulation (P = 0.07). Lower CCL22 levels were recorded at 12 and 24 months (P = 0.03 and P = 0.01) after PHA stimulation. Conclusion and Clinical Relevance Lactobacillus reuteri supplementation decreases allergen responsiveness and may enhance immunoregulatory capacity during infancy. L. reuteri supplementation from week 36 and during the first year of life significantly decreases IgE-associated eczema and lowers allergen and mitogen responsiveness.Funding Agencies|Swedish Research Council|K2011-56X-21854-01-06|Ekhaga Foundation||Olle Engkvist Foundation||Heart and Lung foundation||Research Council for the South-East Sweden|F2000-106|Swedish Asthma and Allergy Association||Cancer and Allergy Association||BioGaia AB, Stockholm, Sweden||University Hospital of Linkoping, Sweden||</p

Differences by occupation in perceived face validity and procedural justice of a common format application of hard biodata and a written job knowledge test

The concept of biodata is defined as an assessment and evaluation of demonstrated to be related to personality structure, personal adjustment, or success in social, educational, or occupational pursuits

Obtaining a Foundation for Nursing Care at the Time of Patient Admission: A Grounded Theory Study

The nursing process can be viewed as a problem-solving model, but we do not know whether use of the whole process including care plans with interventions based on nursing diagnoses improves nurses’ ability to carry out assessments. Therefore, the aim of this study was to illuminate and describe the assessment and decision-making process performed by nurses who formulated individual care plans including nursing diagnosis, goals and interventions or who used standardized care plans when a patient was admitted to their ward for care, and those who did not. Data collection and analysis were carried out by means of Grounded theory. Nurses were observed while assessing patients, after which they were interviewed. The main concern of all nurses was to obtain a foundation for nursing care based on four strategies; building pre-understanding, creating a caring environment, collecting information on symptoms and signs and performing an analysis from different perspectives. It appeared that the most important aspect for nurses who did not employ care plans was the medical reason for the patient’s admission. The nurses who employed care plans discussed their decisions in terms of nursing problems, needs and risks. The results indicate that nurses who formulated care plans were more aware of their professional role

Naiset, miehet ja perussuomalaiset : Sukupuolikuilu, sukupuolenmukainen äänestäminen ja sukupuolistereotypiat perussuomalaisten äänestäjissä

Tutkimuksessa tarkastellaan sukupuoleen liittyviä poliittisia teorioita perussuomalaisten äänestäjissä. Sukupuoliaspekti on aiheellinen perussuomalaisten miesvoittoisuuden ja konservatiivisen arvopohjan perusteella. Tutkimuksessa kartoitetaan ensinnäkin, löytyykö perussuomalaisten nais- ja miesäänestäjien väliltä sukupuolikuilua liittyen sijoittumiseen poliittiselle vasemmisto–oikeisto -akselille. Toiseksi tutkitaan perussuomalaisten nais- ja miesäänestäjien sukupuolenmukaista äänestämisestä ja lopuksi huomio kohdistetaan sukupuolistereotypioiden tarkasteluun perussuomalaisten äänestäjissä. Tutkimusaineistona on kansallinen eduskuntavaalitutkimusaineisto, joka on kerätty vuoden 2011 eduskuntavaalien jälkeen. Tutkimuksen menetelmät ovat kvantitatiivisia: keskeisimpinä menetelminä käytetään ristiintaulukointia, keskiarvotarkastelua sekä logistista regressioanalyysiä. Moderni sukupuolikuiluteoria, jonka mukaan naisäänestäjät ovat miesäänestäjiä vasemmistolaisempia, ei saa tulosten perusteella vahvistusta. Sen sijaan perussuomalaisia miesäänestäjiä voidaan tulosten valossa pitää keskimääräistä miesäänestäjää vasemmistolaisempina. Toiseksi perussuomalaisten nais- ja miesäänestäjillä on valintaa ohjaava sukupuolimieltymys äänestää miespuolista ehdokasta. Tässä suhteessa perussuomalaisten äänestäjät eroavat muiden puolueiden äänestäjistä. Lopuksi tulokset osoittavat, että tietyt sukupuolistereotypiat ovat osa perussuomalaisten äänestäjiä. Stereotypiat miehistä parempina päätöksentekijöinä ja parempina talouspolitiikan ja maahanmuuttopolitiikan käsittelijöinä selittävät puoluevalintaa. Perussuomalaisten naisäänestäjien osalta kuitenkin ainoastaan stereotypia miehistä parempina maahanmuuttopolitiikassa on tilastollisesti merkitsevä. Tutkimuksessa pohditaan selityksiä perussuomalaisten miesäänestäjien vasemmistolaisuuteen sekä stereotypioiden vaikutusta perussuomalaisten äänestäjien valintaa ohjaavaan sukupuolimieltymykseen äänestää miespuolista ehdokasta. Jos sukupuolistereotypiat selittävät perussuomalaisten naisäänestäjien valintaa ohjaavaa sukupuolimieltymystä, perussuomalaisia naisäänestäjiä voidaan pitää poikkeuksellisina äänestäessään ennemmin konservatiivisten arvojen kuin sosiaalikysymysten perusteella. Tuloksista huokuu ensinnäkin perussuomalaisen puolueen maskuliinisuus ja traditionalismi, mutta toisaalta puolueen äänestäjät ovat suhteellisen maltillisia poliittisella vasemmisto–oikeisto –akselilla. Perussuomalainen puolue on onnistunut yhdistämään poliittisen työväenluokkaisen vasemmiston sekä konservatiivisen oikeiston. Tutkimus antaa uutta tietoa perussuomalaisten nais- ja miesäänestäjistä. Yllättävimmät tulokset ovat perussuomalaisten miesäänestäjien vasemmistolaisuus ja perussuomalaisten naisäänestäjien valintaa ohjaava sukupuolimieltymys. Sukupuolistereotypioiden osalta tulokset eivät ole kovin yllättäviä, mutta ainutkertaisia ja erittäin merkittäviä nykypäivänä, koska perussuomalaisten äänestäjät ajattelevat muiden puolueiden äänestäjiä todennäköisemmin miesten olevan naisia parempia politiikassa, joten perinteisiä sukupuolistereotypioita voidaan pitää osana perussuomalaisten äänestäjien puolueidentifikaatiota. Tulokset osoittavat, että perinteisiä sukupuolistereotypioita politiikassa on edelleen olemassa ja ne eroavat puolueen mukaan, joten sukupuoleen liittyvät poliittiset ongelmat ovat ajankohtaisia ja aiheuttavat edelleen poliittista vastakkainasettelua

Type IV Pili in Francisella – A Virulence Trait in an Intracellular Pathogen

Francisella tularensis is a highly virulent intracellular human pathogen that is capable of rapid proliferation in the infected host. Mutants affected in intracellular survival and growth are highly attenuated which highlights the importance of the intracellular phase of the infection. Genomic analysis has revealed that Francisella encodes all genes required for expression of functional type IV pili (Tfp), and in this focused review we summarize recent findings regarding this system in the pathogenesis of tularemia. Tfp are dynamic adhesive structures that have been identified as major virulence determinants in several human pathogens, but it is not obvious what role these structures could have in an intracellular pathogen like Francisella. In the human pathogenic strains, genes required for secretion and assembly of Tfp and one pilin, PilA, have shown to be required for full virulence. Importantly, specific genetic differences have been identified between the different Francisella subspecies where in the most pathogenic type A variants all genes are intact while several Tfp genes are pseudogenes in the less pathogenic type B strains. This suggests that there has been a selection for expression of Tfp with different properties in the different subspecies. There is also a possibility that the genetic differences reflect adaptation to different environmental niches of the subspecies and plays a role in transmission of tularemia. This is also in line with recent findings where Tfp pilins are found to be glycosylated which could reflect a role for Tfp in the environment to promote survival and transmission. We are still far from understanding the role of Tfp in virulence and transmission of tularemia, but with the genomic information and genetic tools available we are in a good position to address these issues in the future

Factors and Conditions that Influence the Implementation of Standardized Nursing Care Plans

Rationale and aim: There is a lack of evidence about how to successfully implement standardized nursing care plans (SNCP) in various settings. The aim of this study was to use the “Promotion Action on Research Implementation in Health Services framework” (PARIHS) to explore important factors and conditions at hospital wards that had implemented SNCPs. Method. We employed a retrospective, cross-sectional design and recruited nurses from four units at a rural hospital and seven units at a university hospital in the western and southern region of Sweden where SNCPs had been implemented. Outcome was measured by means of a questionnaire based on the PARIHS-model. Result: In total, 137 nurses participated in the study. The main factors that had motivated the nurses to implement SNCPs were that they were easy to understand and follow as well as corresponding to organisational norms. The SNCPs were normally based on clinical experience, although research more frequently formed the basis of the SNCPs at the university hospital. Internal facilitators acted as important educators, who provided reminders to use the SNCP and feedback to the SNCP users. The patient experience was not considered valuable. Those who claimed that the implementation was successful were generally more positive in all measurable aspects. The use of SNCPs was rarely evaluated. Conclusions: Clinical experience was considered important by the nurses, while they attributed little value to the patient experiences. Successful implementation of research based SNCPs requires internal facilitators with knowledge of evidence-based nursing