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Competing Interests: Conflict of interest: K.K. is a full-time employee of GE HealthCare.

Phenol-soluble modulins (PSMs) are key virulence factors of S. aureus , and they comprise the structural scaffold of biofilm as they self-assemble into functional amyloids. They have been shown to interact with cell membranes as they display toxicity towards human cells through cell lysis, with αPSM3 being the most cytotoxic. In addition to causing cell lysis in mammalian cells, PSMs have also been shown to interact with bacterial cell membranes through antimicrobial effects. Here, we present a study on the effects of lipid bilayers on the aggregation mechanism of αPSM using chemical kinetics to study the effects of lipid vesicles on the aggregation kinetics and using circular dichroism (CD) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM) to investigate the corresponding secondary structure of the aggregates. We found that the effects of lipid bilayers on αPSM aggregation were not homogeneous between lipid type and αPSM peptides, although none of the lipids caused changes in the dominating aggregation mechanism. In the case of αPSM3, all types of lipids slowed down aggregation to a varying degree, with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) having the most pronounced effect. For αPSM1, lipids had opposite effects, where DOPC decelerated aggregation and lipopolysaccharide (LPS) accelerated the aggregation, while 1,2-dioleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DOPG) had no effect. For αPSM4, both DOPG and LPS accelerated the aggregation, but only at high concentration, while DOPC showed no effect. None of the lipids was capable of inducing aggregation of αPSM2. Our data reveal a complex interaction pattern between PSMs peptides and lipid bilayers that causes changes in the aggregation kinetics by affecting different kinetic parameters along with only subtle changes in morphology.

Introduction: Low socioeconomic status (SES) is associated with poor mental health and cognitive function. Individual-level SES and area-level SES (ASES) may affect mental health and cognitive function through lifestyle. We aimed to quantify the associations of ASES with mental health and cognitive function and examine the mediating role of lifestyle behaviours independent of individual-level SES in a Norwegian population., Methods: In this cross-sectional study, we included 7211 participants (54% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) from Statistics Norway at the geographical subdivision level. Tromsø7 data were used as mediators (smoking, snuff, alcohol, physical activity, diet) and outcomes (cognitive function, anxiety, depression, insomnia). Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex., Results: Higher ASES was associated with better cognitive function and fewer depression and insomnia symptoms, independent of individual-level SES. These associations were mediated by smoking and physical activity. Alcohol was a mediator for depression and cognitive function in women. Age was a significant moderator of the association between ASES and global cognitive function in women. The largest total indirect effect of ASES was found for depression, with the joint effect of the mediators accounting for 36% of the total effect., Conclusions: People living in areas with lower ASES are at higher risk of poor mental health, such as depression and insomnia, and have lower cognitive function possibly due to unhealthy lifestyle (smoking, alcohol and physical inactivity)., Competing Interests: Competing interests: M-LL has received lecture fees from Sanofi, BMS/Pfizer and Bayer not related to this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Cardiovascular disease (CVD) is a leading cause of death and disability and living in areas with low socio-economic status (SES) is associated with increased risk of CVD. Lifestyle factors such as smoking, physical inactivity, an unhealthy diet and harmful alcohol use are main risk factors that contribute to other modifiable risk factors, such as hypertension, raised blood cholesterol, obesity, and diabetes. The potential impact of area-level socio-economic status (ASES) on metabolic CVD risk factors via lifestyle behaviors independent of individual SES has not been investigated previously., Aims: To estimate associations of ASES with CVD risk factors and the mediating role of lifestyle behaviors independent of individual-level SES., Methods: In this cross-sectional study, we included 19,415 participants (52% women) from the seventh survey of the Tromsø Study (2015-2016) (Tromsø7). The exposure variable ASES was created by aggregating individual-level SES variables (education, income, housing ownership) at the geographical subdivision level. Individual-level SES data and geographical subdivision of Tromsø municipality (36 areas) were obtained from Statistics Norway. Variables from questionnaires and clinical examinations obtained from Tromsø7 were used as mediators (smoking, snuff, alcohol, and physical activity), while the outcome variables were body mass index (BMI), total/high-density lipoprotein (HDL) cholesterol ratio, waist circumference, hypertension, diabetes. Mediation and mediated moderation analysis were performed with age as a moderator, stratified by sex., Results: ASES was significantly associated with all outcome variables. CVD risk factor level declined with an increase in ASES. These associations were mediated by differences in smoking habits, alcohol use and physical activity. The associations of ASES with total/HDL cholesterol ratio and waist circumference (women) were moderated by age, and the moderating effects were mediated by smoking and physical activity in both sexes. The largest mediated effects were seen in the associations of ASES with total/HDL cholesterol ratio, with the mediators accounting for 43% of the observed effects., Conclusions: Living in lower SES areas is associated with increased CVD risk due to unhealthy lifestyle behaviors, such as smoking, alcohol use and physical inactivity. These associations were stronger in women and among older participants., Competing Interests: None., (© 2022 The Authors.)

Background: OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial initiated in November 2020. Skull remodeling surgery consists of five burrholes, each 15 mm in diameter, directly over the tumor resection cavity. Preclinical research indicates that this procedure enhances the effect of Tumor Treating Fields considerably. We recently concluded a phase 1 safety/feasibility trial that indicated improved overall survival and no additional toxicity. This phase 2 trial aims to validate the efficacy of the proposed intervention., Methods: The trial is designed as a comparative, 1:1 randomized, minimax two-stage phase 2 with an expected 70 patients to a maximum sample size of 84 patients. After 12-months follow-up of the first 52 patients, an interim futility analysis will be performed. The two trial arms will consist of either a) TTFields therapy combined with best physicians choice oncological treatment (control arm) or b) skull remodeling surgery, TTFields therapy and best practice oncology (interventional arm). Major eligibility criteria include age ≥ 18 years, 1st recurrence of supratentorial glioblastoma, Karnofsky performance score ≥ 70, focal tumor, and lack of significant co-morbidity. Study design aims to detect a 20% increase in overall survival after 12 months (OS12), assuming OS12 = 40% in the control group and OS12 = 60% in the intervention group. Secondary endpoints include hazard rate ratio of overall survival and progression-free survival, objective tumor response rate, quality of life, KPS, steroid dose, and toxicity. Toxicity, objective tumor response rate, and QoL will be assessed every 3rd month. Endpoint data will be collected at the end of the trial, including the occurrence of suspected unexpected serious adverse reactions (SUSARs), unacceptable serious adverse events (SAEs), withdrawal of consent, or loss-to-follow-up., Discussion: New treatment modalities are highly needed for first recurrence glioblastoma. Our proposed treatment modality of skull remodeling surgery, Tumor Treating Fields, and best practice medical oncological therapy may increase overall survival significantly., Trial Registration: ClinicalTrials.gov Identifier: NCT0422399 , registered 13. January 2020., (© 2021. The Author(s).)

WHAT IS KNOWN ON THIS SUBJECT?: There is a need to shed light on healthcare professionals' reactions to the use of the Guided Self-Determination method in a mental health hospital to better understand and adjust the implementation process of evidence-based practice. Healthcare professionals´ values and beliefs play an important role when implementing evidence-based practice in real-world healthcare settings. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The study identifies opposite positions in mental healthcare professionals: being ready or resistant to change when implementing an evidence-based intervention. The positions are elaborated in four thematic dynamic continuums describing reactions to using the intervention. In addition, this is the first study to explore mental healthcare professionals´ reactions to using the Guided Self-Determination method in a mental health context. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: When preparing implementation of an evidence-based intervention, it is important to consider adaptation of the intervention, the mental healthcare professionals' acceptability, support from management and participation in supervision. In future research, it is important to consider collecting data from mental healthcare professionals trained in using an evidence-based intervention, however not using it in clinical practice, to understand barriers towards evidence-based practice. ABSTRACT: Introduction Evidence-based interventions are required in mental health nursing to improve quality and outcome for patients. However, there is a need to shed light on professionals' reactions to the use of evidence-based interventions to better understand and adjust the implementation process. Aim To explore mental healthcare professionals´ reactions to using the evidence-based intervention Guided Self-Determination method in the care of inpatients with severe mental illness. Method A qualitative study conducted in relation to an 8 months implementation program. Data collection: 9 qualitative interviews and field notes generated from supervision of the intervention. Results Four themes emerged from a thematic analysis: "The expert becomes novice," "Theory used as a looking glass," "Guided Self-Determination perceived as an interruption" and "Becoming an informer of the impact of GSD." Discussion Using the themes may help leaders or researchers predict or discover the support needed by individual professionals. Implications for practice When preparing implementation of an evidence-based intervention, it is important to consider adaptation and acceptability, as well as support from management and participation in supervision. Finally, it is worth to consider collecting data from trained professionals, who did not use the intervention in practice to understand barriers towards evidence-based practise., (© 2018 John Wiley & Sons Ltd.)

Severe valvular regurgitation can lead to pulmonary hypertension, atrial fibrillation and heart failure. Vena contracta width is used to estimate the severity of the regurgitation. Parameters affecting visualization of color Doppler have a significant impact on the measurement. We propose a data-driven method for automated adjustment of color gain based on the peak power of the color Doppler signal in the vicinity of the vena contracta. A linear regression model trained on the peak power was used to predict the orifice diameter. According to our study, the color gain should be set to about 6 dB above where color Doppler data completely disappears from the image. Based on our method, orifices with reference diameters of 4, 6.5 and 8.5 mm were estimated with relative diameter errors within 18%, 12% and 14%, respectively., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Background: Caring practice in nursing homes is a complex topic, especially the challenges of meeting the basic needs of residents when their behaviour evokes difficult emotions. Cognitive and physical changes related to aging and disability can contribute to behaviours considered to be unacceptable. For example, resident behaviours such as spitting, making a mess with food or grinding teeth are behaviours that most people do not want to see, hear or experience. The aim of this study was to gain a deeper understanding of how nursing home staff members deal with such behaviours in care situations., Methods: This article draws on ethnographic data to describe how nursing home staff members manage unpleasant resident behaviours. The study was based on two long-term units in two Norwegian public nursing homes. The Region's Medical Ethics Committee and the Norwegian Social Science Data Services granted approval. In total, 45 participants (37 nursing aides and eight nurses) agreed to participate in this study. Ten of the participants were interviewed at the end of the field study., Results: This study indicates that nursing home staff members experience difficult emotions related to some residents' behaviours. However, they found these feelings difficult to express and rarely verbalized them openly. In addition, they were characterized by a strong obligation to help all residents, despite their own feelings. Therefore, it appears that an inner struggle occurs as a part of everyday practice., Conclusions: Despite these difficult emotions, nursing staff members believed that they needed to manage their responses and continued to offer good care to all residents. These findings extend our understanding of this unarticulated part of nursing home practice.

The aim of this study was to gain a deeper understanding of the experience of time when living with severe incurable disease. A phenomenological and philosophical approach of description and deciphering were used. In our modern health care system there is an on-going focus on utilizing and recording the use of time, but less focus on the patient's experience of time, which highlights the need to explore the patients' experiences, particularly when life is vulnerable and time is limited. The empirical data consisted of 26 open-ended interviews with 23 participants receiving palliative care at home, in hospital or in a nursing home in Norway. The theoretical frameworks used are mainly based upon K. Martinsens philosophy of care, K. E. Løgstrup phenomenological philosophy, in addition to C. Saunders' hospice philosophy, L. Feigenberg's thanatology and U. Qvarnström's research exploring patient's reactions to impending death. Experience of time is described as being a movement that moves the individual towards death in the field of opposites, and deciphered to be a universal, but a typical and unique experience emerging through three integrated levels: Sense of time; where time is described as a movement that is proceeding at varying speeds. Relate to time; where the awareness of limited life changes the understanding of time to be more existential. Being in time; where limited time seems to clarify the basic living conditions and phenomena of life. The existence of life when the prospect of death is present is characterized by emotional swings that move within polarizing dimensions which is reflected in the experience of time illustrated as the moves of the pendulum in a grandfather clock. The diversity of the experience of time is oscillating between going fast or slow, being busy or calm, being unpredictable but predictable, safe or unsafe and between being good or bad, depending on the embodied situation of the individual.

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.

To simplify the medical ultrasound system and reduce the cost, several techniques have been proposed to reduce the interconnections between the ultrasound probe and the back-end console. Among them, subaperture processing (SAP) is the most straightforward approach and is widely used in commercial products. This paper reviews the most important error sources of SAP, such as static focusing, delay quantization, linear delay profile, and coarse apodization, and the impacts introduced by these errors are shown. We propose to use main lobe coherence loss as a simple classification of the quality of the beam profile for a given design. This figure-ofmerit (FoM) is evaluated by simulations with a 1-D ultrasound subaperture array setup. The analytical expressions and the coherence loss can work as a quick guideline in subaperture design by equalizing the merit degradations from different error sources, as well as minimizing the average or maximum loss over ranges. For the evaluated 1-D array example, a good balance between errors and cost was achieved using a subaperture size of 5 elements, focus at 40 mm range, and a delay quantization step corresponding to a phase of π/4.

The aim of this study is to describe the experience of time as it presents itself at the place being situated when living with severe incurable disease and receiving palliative care. The empirical data consist of 26 open-ended interviews with 23 patients receiving palliative care at home, at a palliative day care, in a palliative bed unit in hospital or in a nursing home in Norway. A common meaning of a shifting space for living emerged from the analysis and was revealed through three different aspects: (i) Transition from a predictable to an unpredictable time: To live with severe incurable disease marks a transition to a changed life involving an ongoing weakened and altered body with bothersome symptoms making experience of time different and unpredictable. (ii) Transition between a safe and unsafe time: When time is unpredictable, feeling safe is revealed as essential to how time is experienced at the place being situated. (iii) To be in transition from a homely to a homeless existence: In a time of increased bodily weakness, unpredictable ailments and displacements, the sense of belonging to the place is revealed as significant to the experience of time. Not knowing where to be in a time of change is like an existential cry of distress where the foothold in existence is lost. The findings are discussed and interpreted as an embodied experience originating from the passage of time continually affecting life sometimes so fundamentally that it marks a transition to a changed space of life that is reflected in the experience of time., (© 2013 Nordic College of Caring Science.)

Background: Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in the devastating brain tumor glioblastoma multiforme (GBM). bCSC are proposed a central role in tumor initiation, progression, treatment resistance and relapse and as such present a promising target in GBM research. The Notch signaling pathway is often deregulated in GBM and we have previously characterized GBM-derived bCSC cultures based on their expression of the Notch-1 receptor and found that it could be used as predictive marker for the effect of Notch inhibition. The aim of the present project was therefore to further elucidate the significance of Notch pathway activity for the tumorigenic properties of GBM-derived bCSC., Methods: Human-derived GBM xenograft cells previously established as NSC-like neurosphere cultures were used. Notch inhibition was accomplished by exposing the cells to the gamma-secretase inhibitor DAPT prior to gene expression analysis and intracranial injection into immunocompromised mice., Results: By analyzing the expression of several Notch pathway components, we found that the cultures indeed displayed different Notch pathway signatures. However, when DAPT-treated neurosphere cells were injected into the brain of immunocompromised mice, no increase in survival was obtained regardless of Notch pathway signature and Notch inhibition. We did however observe a decrease in the expression of the stem cell marker Nestin, an increase in the proliferative marker Ki-67 and an increased number of abnormal vessels in tumors formed from DAPT-treated, high Notch-1 expressing cultures, when compared with the control., Conclusion: Based on the presented results we propose that Notch inhibition partly induces differentiation of bCSC, and selects for a cell type that more strongly induces angiogenesis if the treatment is not sustained. However, this more differentiated cell type might prove to be more sensitive to conventional therapies.

Objectives: Brain tumor imaging is challenging. Although 18F-FET PET is widely used in the clinic, the value of 18F-FET MicroPET to evaluate brain tumors in xenograft has not been assessed to date. The aim of this study therefore was to evaluate the performance of in vivo 18F-FET MicroPET in detecting a treatment response in xenografts. In addition, the correlations between the 18F-FET tumor accumulation and the gene expression of Ki67 and the amino acid transporters LAT1 and LAT2 were investigated. Furthermore, Ki67, LAT1 and LAT2 gene expression in xenograft and archival patient tumors was compared., Methods: Human GBM cells were injected orthotopically in nude mice and 18F-FET uptake was followed by weekly MicroPET/CT. When tumor take was observed, mice were treated with CPT-11 or saline weekly. After two weeks of treatment the brain tumors were isolated and quantitative polymerase chain reaction were performed on the xenograft tumors and in parallel on archival patient tumor specimens., Results: The relative tumor-to-brain (T/B) ratio of SUV max was significantly lower after one week (123 ± 6%, n = 7 vs. 147 ± 6%, n = 7; p = 0.018) and after two weeks (142 ± 8%, n = 5 vs. 204 ± 27%, n = 4; p = 0.047) in the CPT-11 group compared with the control group. Strong negative correlations between SUV max T/B ratio and LAT1 (r = -0.62, p = 0.04) and LAT2 (r = -0.67, p = 0.02) were observed. In addition, a strong positive correlation between LAT1 and Ki67 was detected in xenografts. Furthermore, a 1.6 fold higher expression of LAT1 and a 23 fold higher expression of LAT2 were observed in patient specimens compared to xenografts., Conclusions: 18F-FET MicroPET can be used to detect a treatment response to CPT-11 in GBM xenografts. The strong negative correlation between SUV max T/B ratio and LAT1/LAT2 indicates an export transport function. We suggest that 18F-FET PET may be used for detection of early treatment response in patients.

Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor among adults. Despite recent treatment progress, most patients succumb to their disease within 2 years of diagnosis. Current research has highlighted the importance of a subpopulation of cells, assigned brain cancer stem-like cells (bCSC), to play a pivotal role in GBM malignancy. bCSC are identified by their resemblance to normal neural stem cells (NSC), and it is speculated that the bCSC have to be targeted in order to improve treatment outcome for GBM patients. One hallmark of GBM is aberrant expression and activation of the epidermal growth factor receptor (EGFR) and expression of a deletion variant EGFRvIII. In the normal brain, EGFR is expressed in neurogenic areas where also NSC are located and it has been shown that EGFR is involved in regulation of NSC proliferation, migration, and differentiation. This led us to speculate if EGFR and EGFRvIII are involved in the regulation of bCSC. In this study we use GBM neurosphere cultures, known to preserve bCSC features. We demonstrate that EGFR and EGFRvIII are downregulated upon differentiation and moreover that when EGFR signaling is abrogated, differentiation is induced. Furthermore, we show that differentiation leads to decreased tumorigenic and stem cell-like potential of the neurosphere cultures and that by specifically inhibiting EGFR signaling it is possible to target the bCSC population. Our results suggest that differentiation therapy, possibly along with anti-EGFR treatment would be a feasible treatment option for patients with GBM, by targeting the bCSC population.

A nursing home is a complex multifactorial environment that influences the decisions and actions of nursing staff. Many of the actions performed by nursing staff appear to be straightforward or simple because they are repetitive, encompassing everyday activities such as helping a resident to get up in the morning, shower or get dressed. These daily activities are usually performed smoothly as part of normal care. This article draws on ethnographic data from a study of caring practices in a nursing home with the aim of investigating how a seemingly ordinary, but unexpected, event can develop into a chaotic situation. Staff appeared to have difficulty managing the situation, and they seemed to be disorganized in the application of their skills. First, we describe the situation in detail before investigating and discussing the situation to provide a deeper understanding of the complexity of nursing home practice., (© 2013 Wiley Publishing Asia Pty Ltd.)

Background: Brain cancer stem-like cells (bCSC) are cancer cells with neural stem cell (NSC)-like properties found in glioblastoma multiforme (GBM) and they are assigned a central role in tumor initiation, progression and relapse. The Notch pathway is important for maintenance and cell fate decisions in the normal NSC population. Notch signaling is often deregulated in GBM and recent results suggest that this pathway plays a significant role in bCSC as well. We therefore wished to further elucidate the role of Notch activation in GBM-derived bCSC., Methods: Human-derived GBM xenograft cells were cultured as NSC-like neurosphere cultures. Notch modulation was accomplished either by blocking the pathway using the γ-secretase inhibitor DAPT or by activating it by transfecting the cells with the constitutive active Notch-1 receptor., Results: GBM neurosphere cultures with high endogenous Notch activation displayed sensitivity toward Notch inhibition with regard to tumorigenic features as demonstrated by increased G0/G1 population and reduced colony formation capacity. Of the NSC-like characteristics, only the primary sphere forming potential was affected, while no effect was observed on self-renewal or differentiation. In contrast, when Notch signaling was activated a decrease in the G0/G1 population and an enhanced capability of colony formation was observed, along with increased self-renewal and de-differentiation., Conclusion: Based on the presented results we propose that active Notch signaling plays a role for cell growth and stem cell-like features in GBM neurosphere cultures and that Notch-targeted anti-bCSC treatment could be feasible for GBM patients with high endogenous Notch pathway activation.

Why are bodily washing practices the way they are in nursing? Michel Foucault argues that modern democratic societies discipline human bodies in accordance with political interests. In the extension of that argumentation we will show that bodily cleanliness in modern nursing may have been used as a disciplining tool. The first part of our discussion takes as its point of departure the second half of the 19th/the beginning of the 20th centuries, the period in which modern nursing emerged. At that time scientific theories on hygiene seem to have legitimized the political effort to produce a clean, pleasant-smelling, decent, obedient, and productive population. Doctors, nurses and teachers played important roles in the implementation of hygienic bodily washing practices. The second part of the discussion focuses on the post-war period. At that time humanistic needs theories seem to have legitimized political argumentation for independent patients who washed themselves if possible. Those who could not manage on their own, should, as far as possible, be washed by cheaper staff, so that nurses could concentrate on medical treatment. Finally we argue that present day bodily washing practices in nursing are in accordance with the norms of appearance and smell that arose in the second half of the 19th and the first part of the 20th centuries. We further argue that staff with little or no education perform much of the bodily nursing work. Self-care seems to be of interest only when it reduces public expenses., (© 2013 Blackwell Publishing Ltd.)

This article presents findings from a phenomenological study exploring experience of time by patients living close to death. The empirical data consist of 26 open-ended interviews from 23 patients living with severe incurable disease receiving palliative care in Norway. Three aspects of experience of time were revealed as prominent: (i) Entering a world with no future; living close to death alters perception of and relationship to time. (ii) Listening to the rhythm of my body, not looking at the clock; embodied with severe illness, it is the body not the clock that structures and controls the activities of the day. (iii). Receiving time, taking time; being offered - not asked for - help is like receiving time that confirms humanity, in contrast to having to ask for help which is like taking others time and thereby revealing own helplessness. Experience of time close to death is discussed as an embodied experience of inner, contextual, relational dimensions in harmony and disharmony with the rhythm of nature, environment and others. Rhythms in harmony provide relief, while rhythms in disharmony confer weakness and limit time., (© 2012 The Authors. Scandinavian Journal of Caring Sciences © 2012 Nordic College of Caring Science.)

Background: Western governments have initiated reforms to improve the quality of care for nursing home residents. Most of these reforms encompass the use of regulations and national quality indicators. In the Norwegian context, these regulations comprise two pages of text that are easy to read and understand. They focus particularly on residents' rights to plan their day-to-day life in nursing homes. However, the research literature indicates that the implementation of the new regulations, particularly if they aim to change nursing practice, is extremely challenging. The aim of this study was to further explore and describe nursing practice to gain a deeper understanding of why it is so hard to implement the new regulations., Methods: For this qualitative study, an ethnographic design was chosen to explore and describe nursing practice. Fieldwork was conducted in two nursing homes. In total, 45 nurses and nursing aides were included in participant observation, and 10 were interviewed at the end of the field study., Results: Findings indicate that the staff knew little about the new quality regulations, and that the quality of their work was guided by other factors rooted in their nursing practice. Further analyses revealed that the staff appeared to be committed to daily routines and also that they always seemed to know what to do. Having routines and always knowing what to do mutually strengthen and enhance each other, and together they form a powerful force that makes daily nursing care a taken-for-granted activity., Conclusion: New regulations are challenging to implement because nursing practices are so strongly embedded. Improving practice requires systematic and deeply rooted practical change in everyday action and thinking.

Human brain tumors are a heterogenous group of neoplasms occurring inside the cranium and the central spinal cord. In adults and children, astrocytic glioma and medulloblastoma are the most common subtypes of primary brain tumors. These tumor types are thought to arise from cells in which Notch signaling plays a fundamental role during development. Recent findings have shown that Notch signaling is dysregulated and contributes to the malignant potential of these tumors. Growing evidence point towards an important role for cancer stem cells in the initiation and maintenance of glioma and medulloblastoma. In this chapter we will cover the present findings of Notch signaling in human glioma and medulloblastoma and try to create an overall picture of its relevance in the pathogenesis of these tumors.

Glioblastoma multiforme (GBM) is the most common, and most aggressive primary brain tumor among adults. A vast majority of the tumors express high levels of the epidermal growth factor receptor (EGFR) as a consequence of gene amplification. Furthermore, gene amplification is often associated with mutation of EGFR, and the constitutive activated deletion variant EGFRvIII is the most common EGFR mutation found in GBM. Activated EGFR signaling, through overexpression and/or mutation, is involved in increased tumorigenic potential. As such, EGFR is an attractive target for GBM therapy. However, clinical studies with EGFR inhibitors have shown inconsistent results, and as such, further knowledge regarding the role of EGFR and EGFRvIII in GBM is needed. For this, an appropriate in vivo/in vitro tumor model is required. Here, we report the establishment of an experimental GBM model in which the expressions of EGFR and EGFRvIII are maintained both in xenograft tumors growing subcutaneously on mice and in cell cultures established in stem cell conditions. With this model it will be possible to further study the role of EGFR and EGFRvIII, and response to targeted therapy, in GBM., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Women (n = 87) at women's shelters in Norway, a country of high welfare and gender equality, reported a multitude of severe threats and actual acts of physical, sexual and psychological violence. An individual threatening to kill his partner represented a significant increased risk for experiencing serious acts of violence, especially when the threats were repeated. A self-administered questionnaire was sent to all the women's shelters. Experiences of violence were measured by The Severity of Violence against Women Scale (SVAWS) and the Psychological Maltreatment of Women Index (PMWI).

Background: In recent years, physical therapists have paid greater attention to body awareness. Clinicians have witnessed the benefits of supporting their patients' learning of movement awareness through the promotion of their movement quality., Objective: The aim of this study was to investigate how physical therapist experts promote movement quality in their usual clinical settings., Design: A phenomenological research design that included a sampling strategy was devised. Using specific criteria, 6 lead physical therapists nominated a group of physical therapist experts from the fields of neurology, primary health care, and mental health. Fifteen informants, 5 from each field, agreed to participate., Methods: In-depth interviews were conducted with a semistructured interview guide. The informants were invited to simply describe what they had experienced to be successful therapeutic processes for promoting movement quality. Each interview was audiotaped and transcribed. The data analysis was based on a multistep model., Results: Three main themes emerged from the data. First, the physical therapists' embodied presence and movement awareness served as a precondition and an orientation for practice. Embodied presence is a bodily felt sense, a form of personal knowing that evokes understanding and fosters meaning. Second, creating a platform for promoting movement quality revealed implementation of psychological attitudes. Third, action strategies for promoting movement quality suggested a movement awareness learning cycle and components for clinical use., Conclusions: This study demonstrated specific attitudes and skills used by physical therapist experts to promote movement quality in their clinical practice. These results may serve as a therapeutic framework for promoting movement quality in clinical physical therapy, although further research is needed.

In color flow imaging for medical diagnosis, the inherent trade-off between frame rate and image quality may often lead to suboptimal images. Parallel receive beamforming is used to help overcome this problem, but this introduces artifacts in the images. In addition to the parallel beamforming artifacts found in B-mode imaging, we have found that a difference in curvature of transmit and receive beams gives a bias in the Doppler velocity estimates. This bias causes a discontinuity in the velocity estimates in color flow images. In this work, we have shown that interpolation of the autocorrelation estimates obtained from overlapping receive beams can reduce these artifacts significantly. Because the autocorrelation function varies quite slowly, the beams can be acquired with a considerable time difference, for instance across interleaving groups or across scan planes in a 3-D scan. We have shown that a high frame rate of color flow images can be maintained with parallel beam acquisition with minimal deterioration of the image quality.

Gliomas are among the most devastating adult tumors for which there is currently no cure. The tumors are derived from brain glial tissue and comprise several diverse tumor forms and grades. Recent reports highlight the importance of cancer-initiating cells in the malignancy of gliomas. These cells have been referred to as brain cancer stem cells (bCSC), as they share similarities to normal neural stem cells in the brain. The Notch signaling pathway is involved in cell fate decisions throughout normal development and in stem cell proliferation and maintenance. The role of Notch in cancer is now firmly established, and recent data implicate a role for Notch signaling also in gliomas and bCSC. In this review, we explore the role of the Notch signaling pathway in gliomas with emphasis on its role in normal brain development and its interplay with pathways and processes that are characteristic of malignant gliomas.

The number of patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased rapidly in Copenhagen, Denmark since 2003. Patients with the typical Panton-Valentine leukocidin-positive CA-MRSA clone ST30-IVc were contacted with the aim of treating MRSA carriers, evaluating the effect of MRSA eradication therapy (ET), and finding links among patients. Twenty-three index patients infected with the ST30-IVc clone from November 2003 to September 2005 were contacted and transmission chains were studied. The majority of ST30-IVc patients had a connection to the Philippines. Household members were screened for MRSA and all members of families with MRSA carriers were offered treatment of the carrier state and were followed for 1 year. MRSA carriers were found in seven of 16 households and transmission occurred among close contacts and in kindergartens. Five days of ET was insufficient and at least one person in each household was treated with systemic antibiotics. All families were MRSA negative at 1-year follow-up. The CA-MRSA clone ST30-IVc has been imported to Copenhagen, Denmark, primarily from the Philippines, and has spread through close contacts and in kindergartens. Treatment of MRSA carriers was difficult and required many resources, but the clone was eventually successfully eliminated. The import of ST30-IVc to Denmark will continue, but the spread of the clone in Denmark can be kept to a minimum by direct intervention in the affected families.

Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.

Meticillin-resistant Staphylococcus aureus (MRSA) is a major problem in hospitals worldwide. Hand hygiene is recognised as crucial in limiting the spread of MRSA but less is known about the role of MRSA reservoirs in the inanimate hospital environment. We evaluated the effect of hydrogen peroxide vapour diffused by Sterinis((R)) against MRSA in two experimental hospital settings and in two field trials. Dipslides were used for MRSA detection and quantification before and after using the Sterinis disinfection process. In the first experimental hospital setting, four epidemic MRSA strains were placed at five locations and left for one week. All strains survived the week but not the disinfection process. In field trial one 14 upholstered chairs from a department with many MRSA positive patients were left for one month in a closed room prior to disinfection. MRSA was found on the upholstery of four of the 14 chairs. Three chairs became MRSA negative immediately after the disinfection, the fourth 24h later. The second field trial was in the private home of a MRSA positive family of four individuals. One location was found MRSA positive, remaining so after the Sterinis cycles. We found Sterinis to be effective against MRSA in the experimental hospital setting and upholstered chairs, but not in the private home of heavily colonised MRSA patients.

The aim of the study was to identify and describe spouses'/cohabitants' experiences of living with a partner with bipolar affective disorder over time. Qualitative research interviews were conducted with eight spouses/cohabitants. Transcribed interviews were analysed structurally based on Ricoeur's phenomenological hermeneutics as described by Lindseth and Norberg. The participants' shared lives ranged from 6 to 51 years, and the study found three major aspects that characterized their experience along this time-dimension; experience formed part of a cumulative process containing up to 14 experiences. Each experience created a preunderstanding that affected how subsequent experiences were perceived, and mastered. These three major aspects had a reciprocal influence on the following 14 experiences over time: Fear and the incomprehensible. Accusations. Self-doubt and doubt about own powers of judgement. Care and information vs. being overlooked or turned away by health personnel. Stigmatization and loss of social network. Uncertainty, powerlessness and hope. Loneliness. Anger and despair. The persistent threat. Own health problems. Grief over loss. Dawning acceptance. Reconciliation. New hope. A theoretical understanding using gestalt therapy theory suggests that burdensome experience can be seen as an inner imbalance in the spouse/cohabitant when she/he cannot find meaning in their experiences. When only parts of the whole are perceived, an incomplete gestalt is formed in the person's lived-experience that counteracts the equilibrium of the organism. Insight and meaning can protect them against burdensome experiences and nurses can empower them through care, health-promoting education and guidance. Nursing research should develop methods of education and guidance sensitive enough to help each spouse/cohabitant, regardless of where they are in their cumulative process.

Movement quality is a phenomenon frequently used by physiotherapists in oral language, written text, and clinical practice, with little clarification. The purpose was to investigate the lived experiences of a group of expert physiotherapists, searching for essential features and characteristics of the phenomenon. A phenomenological study, using in-depth interviews was chosen. Ten copies of Fine Art were used to stimulate the description of the phenomenon. The informants were 15 peer-designated physiotherapists, five from each field of neurology, psychosomatic/psychiatry and primary health care. They were nominated by physical therapist leaders in the region. The interviews were audiotaped and transcribed. Giorgis' recommendation concerning analysis of the interview data was followed. Four main themes were developed, seeing movement quality as biomechanical, physiological, psycho-socio-cultural, and existential, all interacting processes. Each theme includes preconditions to movement quality and movement characteristics. Movement quality in general was seen as a unifying phenomenon, representing a synthesis of the four themes. The outcome of the study is the Movement Quality Model (MQM) illuminating essential features and characteristics of the phenomenon. Further research is needed for clarification and application in clinical practice.

Objectives: There is a call for a further investigation of Sense of Coherence (SOC), the central concept in salutogenesis, and its relation to health and life satisfaction. No previous studies have investigated the utility of SOC versus mental symptoms for the prediction of life satisfaction among people with chronic mental health problems (MHP)., Methods: The present study has a prospective design including a baseline assessment and a 1-year follow up. We recruited 107 adults from the community health care system. SOC was measured by the Sense of Coherence questionnaire, mental symptoms by the Symptom Checklist-90 revised and life satisfaction by The Quality of Life Scale (all Norwegian versions)., Results: The results show that while SOC predicts change in life satisfaction (standardized beta coefficient for SOC was 0.39, P = 0.014), mental symptoms did not (standardized beta coefficient 0.00, P = 1.0)., Conclusions: These findings emphasize the importance of assessing factors that may explain differences in life satisfaction over and above mental symptoms among people with MHP. The results indicate that improving SOC among people with MHP might provide important opportunities for improving their life satisfaction.

We used the Quality of Life Scale to assess quality of life among 107 Norwegians with chronic mental health problems (MHP) from the community health care system versus 1893 general population adults. The groups differed in quality of life, including broader life domains. Age and quality of life were more strongly positively correlated in the MHP group than in the general population. Mental symptoms (measured by the Symptom Checklist-90 Revised) and quality of life were strongly negatively correlated in the MHP group. Services for people with chronic MHP should focus on enhancing quality of life and on its role as an outcome variable.

This article aims to illustrate how Antonovsky's salutogenic theory and its central concept of sense of coherence can be operationalized into salutogenic therapy principles and an intervention program for promoting a sense of coherence, coping, and mental health among people with mental health problems. The intervention is based on the following five basic components or therapy principles: (1) the health continuum model; (2) the story of the person; (3) health-promoting (salutary) factors; (4) the understanding of tension and strain as potentially health promoting, and (5) active adaptation. The program is a talk therapy group intervention and consists of 16 group meetings and homework. The intervention may serve as a guide to mental health nursing practice when coping is the main target.

Parallel beamforming is frequently used to increase the acquisition rate of medical ultrasound imaging. However, such imaging systems will not be spatially shift invariant due to significant variation across adjacent beams. This paper investigates a few methods of parallel beam-forming that aims at eliminating this flaw and restoring the shift invariance property. The beam-to-beam variations occur because the transmit and receive beams are not aligned. The underlying idea of the main method presented here is to generate additional synthetic transmit beams (STB) through interpolation of the received, unfocused signal at each array element prior to beamforming. Now each of the parallel receive beams can be aligned perfectly with a transmit beam--synthetic or real--thus eliminating the distortion caused by misalignment. The proposed method was compared to the other compensation methods through a simulation study based on the ultrasound simulation software Field II. The results have been verified with in vitro experiments. The simulations were done with parameters similar to a standard cardiac examination with two parallel receive beams and a transmit-line spacing corresponding to the Rayleigh criterion, wavelength times f-number (lambda x f#). From the results presented, it is clear that straightforward parallel beamforming reduces the spatial shift invariance property of an ultrasound imaging system. The proposed method of using synthetic transmit beams seems to restore this important property, enabling higher acquisition rates without loss of image quality.

Background: Nonoperative management (NOM) is an accepted treatment of pediatric solid organ injuries and is typically successful. Blunt pancreatic trauma tends to require operative intervention more frequently. We sought to identify predictors of failure of NOM and compare the outcome of operative management against NOM., Methods: A retrospective analysis was performed from January 1993 to December 2002 of all children with blunt pancreatic injuries from the trauma registries of 7 designated level 1 pediatric trauma centers. Failure of NOM was defined as the need for intraabdominal operative intervention. Injuries were graded I to V, and ductal injury was defined as grades III to V. Parameters included mechanism of injury, injury severity score (ISS), organ grade, Glasgow Coma Scale score, and outcome. Data were analyzed by Fisher exact test and Mann-Whitney U test, with mean values +/- SD and significance of P < .05., Results: Pancreatic injuries were present in 173 (9.2%) of 1823 patients. Of these, 43 (26.0% [43/173]) required an operation. Valid morbidity data was obtained in 118 of 173 patients. ISS was significantly higher in all patients treated operatively. Patients with an injury of grade III to V failed NOM more frequently than all patients with pancreatic injury (P =.0169). Length of stay was longer, and the incidence of pseudocysts, drainage procedures, and pancreatitis was higher in NOM patients, although not significant., Conclusions: Patients with pancreatic injuries had a NOM failure rate of 26.0%. ISS and injury grades III to V were predictors of NOM failure. Patients with pancreatic ductal injury require more aggressive management.

We propose a new algorithm for real-time, adaptive-clutter-rejection filtering in ultrasound color flow imaging (CFI) and related techniques. The algorithm is based on regression filtering using eigenvectors of the signal correlation matrix as a basis for representing clutter, a method that previously has been considered too computationally demanding for real-time processing in general CFI applications. The data acquisition and processing scheme introduced allows for a more localized sampling of the clutter statistics and, therefore, an improved clutter attenuation for lower filter orders. By using the iterative power method technique, the dominant eigenvalues and corresponding eigenvectors of the correlation matrix can be estimated efficiently, rendering real-time operation feasible on desktop computers. A new adaptive filter order algorithm is proposed that successfully estimates the proper dimension of the clutter basis, previously one of the major drawbacks of this clutter-rejection technique. The filter algorithm performance and computational demands has been compared to that of conventional clutter filters. Examples have been included which confirms that, by adapting the clutter-rejection filter to estimates of the clutter-signal statistics, improved attenuation of the clutter signal can be achieved in normal as well as more excessive cases of tissue movement and acceleration.

Objective: Although the theory of salutogenesis provides generic understanding of how coping may be created, this theoretical perspective has not been explored sufficiently within research among people suffering from mental health problems. The aim of this study is to investigate the effect of talk-therapy groups based on salutogenic treatment principles on coping with mental health problems., Method: In an experimental design, the participants (residents in the community) were randomly allocated to a coping-enhancing experimental group (n=59) and a control group (n=47) receiving standard care. Coping was measured using the sense of coherence (SOC) questionnaire., Results: Coping improved significantly in the experiment group (+6 points) compared with the control group (-2 points). The manageability component contributed most to this improvement., Conclusion: Talk-therapy groups based on salutogenic treatment principles improve coping among people with mental health problems., Practice Implications: Talk-therapy groups based on salutogenic treatment principles may be helpful in increasing coping in the recovery process among people with mental health problems and seem to be applicable to people with various mental health problems.

Introduction: We have found an epidemic increase in methicillin-resistant Staphylococcus aureus (MRSA) in Copenhagen. The increase has a complex background and involves hospitals, nursing homes and persons nursed in their own home., Material and Methods: We found 33 MRSA patients in 2003 and 121 in 2004. All isolates have been spa-typed and epidemiologic information collected., Results: The number of MRSA cases has a doubling time of about six months. The epidemic has been caused by many different MRSA types and 31 staphylococcus protein A genotypes (spa types). MRSA has caused several hospital outbreaks and is endemic in 10 nursing homes. Five staff members from nursing homes have been infected with MRSA. MRSA commonly causes skin and soft tissue infections (76%), but serious infections such as septicaemia and pneumonia are also found., Conclusion: Treatment of MRSA-infected patients is costly due to isolation regimes, increase in bed-days and treatment with special antibiotics. After treatment of the infection and in cases of MRSA carriage, MRSA is found on the skin and in the nose. Carriage of MRSA can be eradicated by washing with chlorhexidine and nasal administration of mupirocin. The necessary resources for handling the epidemic are not available. Without active intervention, this situation will have serious implications for the health care system.

The quality of ultrasound color flow images is highly dependent on sufficient attenuation of the clutter signals originating from stationary and slowly moving tissue. Without sufficient clutter rejection, the detection of low velocity blood flow will be poor, and the velocity estimates will have a large bias. In some situations, e.g., when imaging the coronary arteries or when the operator moves the probe in search for small vessels, there is considerable movement of tissue. It has been suggested that clutter rejection can be improved by mixing down the signal with an estimate of the mean frequency prior to high pass filtering. In this paper, we compare this algorithm with several other adaptive clutter filtering algorithms using both experimental data and simulations. We found that realistic accelerations of the tissue have a large effect on the clutter rejection. The best results were obtained by mixing down the signal with non-constant phase increments estimated from the signal. This adapted the filter to a possibly accelerated tissue motion and produced a significant improvement in clutter rejection.

For ultrasound color flow images with high quality, it is important to suppress the clutter signals originating from stationary and slowly moving tissue sufficiently. Without sufficient clutter rejection, low velocity blood flow cannot be measured, and estimates of higher velocities will have a large bias. The small number of samples available (8 to 16) makes clutter filtering in color flow imaging a challenging problem. In this paper, we review and analyze three classes of filters: finite impulse response (FIR), infinite impulse response (IIR), and regression filters. The quality of the filters was assessed based on the frequency response, as well as on the bias and variance of a mean blood velocity estimator using an autocorrelation technique. For FIR filters, the frequency response was improved by allowing a non-linear phase response. By estimating the mean blood flow velocity from two vectors filtered in the forward and backward direction, respectively, the standard deviation was significantly lower with a minimum phase filter than with a linear phase filter. For IIR filters applied to short signals, the transient part of the output signal is important. We analyzed zero, step, and projection initialization, and found that projection initialization gave the best filters. For regression filters, polynomial basis functions provide effective clutter suppression. The best filters from each of the three classes gave comparable bias and variance of the mean blood velocity estimates. However, polynomial regression filters and projection-initialized IIR filters had a slightly better frequency response than could be obtained with FIR filters.

The purpose of this study is to identify central aspects of feelings in relation to the experience of being a brother or sister of someone who suffers from schizophrenia. The study makes use of a hermeneutical method for the collection of data as well as for the systemizing and interpretation of data. The participants in the study were 16 siblings of persons with diagnosed schizophrenia. In total 80 interviews were done, with an average length of 50 min. A theory of interrupted feelings was developed within the tension between empirical data and preunderstanding. Mixed feelings of grief, hope, anger, guilt and shame are interrupted by four interrelated factors: ambiguous loss, the fluctuating nature of the illness, an inner prohibition of feelings and the tendency of others to invalidate the feelings. The interruption may lead to a lonely and painful experience which is difficult both to process for oneself and to share with others.

Objective: The effect of folic acid supplement on the prevalence of congenital anomalies was studied in a Danish population., Material and Methods: From 1983 to 1986 all Danish women resident in the county of Funen were offered free folic acid when pregnant or planning a pregnancy. Folic acid dose was randomised to 2.5 or 1.0 mg. A randomised control group was not feasible for ethical reasons. Hospitals, midwives and most general practitioners cooperated to procure information on close to all pregnancies and congenital anomalies were recorded., Results and Conclusions: In a total of 14,021 pregnancies resulting in child birth 8184 women (58.4%) had folic acid with randomisation. Supplement was started in the randomised group before the last menstrual period in 1359/8184 (16.6%) and in the first 19 weeks of pregnancy in 6825/8184 (83.4%). The prevalence of congenital anomalies was 224 in 8293 children (27.0/1000). No dose-dependent differences were found in either total anomalies or in those specific malformations which have been reported to occur with reduced prevalence with periconceptional folic acid. The result was probably influenced by a start of supplement too late to affect malformation development in many cases and by the high level of both folic acid doses given compared to usual recommendations. Pregnancies without folic acid supplement showed prevalences similar to the supplemented groups.

Objective: The effect of folic acid supplement on the prevalence of congenital anomalies was studied in a Danish population., Material and Methods: From 1983 to 1986 all Danish women resident in the county of Funen were offered free folic acid when pregnant or planning a pregnancy. Data concerning the starting time of folic acid supplement and congenital anomalies were recorded on close to all pregnancies. Children of folic acid supplemented mothers were subdivided as to start of supplement with dividing lines at week 7 and week 11 calculated from the last menstrual period. Structural malformations were subdivided into an early group with malformation development in the first 7 weeks from the last menstrual period and a late group where malformations develop in weeks 8 to 11., Results: In a total of 14,021 pregnancies 10,494 pregnant women (74.8%) had folic acid supplement. No folic acid was taken by 2721 women (19.4%) and in 806 cases (5.8%) information was lacking. The prevalence of congenital anomalies was 380 in 14,185 children (26.7/1000). Children whose mothers started folic acid supplement before the 7th week of pregnancy showed a significantly lower prevalence of the malformations which develop in the first 7 weeks, when compared to pregnancies with a later start of supplement. The result was interpreted as a clearcut trend.

Objective: To determine whether a supplement of folic acid given preconceptionally or early in pregnancy had any influence on, birth weight, incidence of preterm labour, low birth weight and small for gestational age. Furthermore, the aim was to elucidate, whether the outcome differed following the administration of two different dosages of folic acid, namely 2.5 and 1.0 mg., Material: All women in the childbearing age living on the island of Funen, Denmark (population 500,000) were offered a supplement of folic acid over a period of 3 years and 3 months. 14,021 women, who gave birth to 13,860 single-born and 325 multiborn children, were registered. A total of 8184 women took part in the double-blind randomized trial: 2310 had a supplement of folic acid without being randomized and 2721 women received no folic acid supplement. No information regarding the use of folic acid was available in 806 pregnancies. Abortions (512) were excluded., Results and Conclusions: A supplement 1.0 mg folic acid had the same effect as 2.5 mg. The effects of supplementing the diet with folic acid given preconceptionally or in the first half of pregnancy in an affluent Northern country were a slight increase of birth weight and a decrease in the incidence of preterm labour, infants with low birth weight and small for gestational age. The greatest effect was seen in the groups receiving folic acid preconceptionally.

The present study concerns the air quality and microbiological contamination in two newly built operating theatres; one with laminar air flow (LAF) equipment for cardio-thoracic operations, and one with conventional ventilation for urological operations. Both theatres had an identical number of air exchanges (17/h), identical microclimatic conditions and they employed the same cleaning procedures. In the LAF-ventilated operating theatre bacterial contamination of the air was effectively reduced to less than 10 colony-forming units (CFU)/m3 in all 125 samples (1 m3 per sample) tested. In most samples, 118/125, the bacterial count was less than 5 CFU/m3, despite the presence of ten persons. The conventionally ventilated theatre reached values up to 120 CFU/m3 during the most active period of the day when approximately seven persons were present. The LAF ventilation reduced both the content of particles in the air and contamination by bacteria on the floor. In both theatres cleaning procedures had only a low impact on CFU in the air and on the floor. The use of diathermia markedly increased the level of small particles in the air, and this may influence the air quality in the operating theatres.

The aim was to examine how often women referred to office gynaecologists were using self-medication of "natural medicines". By interview-questionnaires 62 gynaecologists asked 5.664 women about their age, name of used natural medicine and how the user felt it helped her. One thousand six hundred and sixty-four used natural medicine with 91 different names. About 75% percent of the users registered one or more effects, characterized as "good for everything", "enhances their wellbeing" "gives more energy", "relieves hot flushes and sweatings", "relieves rheumatic pain", or "is diuretic". The effects seem to be a universal stimulation of the general condition, effectuated either by vitamins and minerals or by placebo-effect. One third of the users of "melbrosia" registered a good effect on climacteric discomfort. It was not possible by laboratory analyses to find any sex-steroids in melbrosia. Nor was it possible to demonstrate biological oestrogenic effect on animals (mice and rats) of this drug in a trial done by Niels Einer-Jensen et al (personal communication).

Objectives: The natural medicines, Cimicifuga and Melbrosia, are widely sold. Cimicifuga is an extract of Cimicifuga racemosa (L.), and Melbrosia is a mixture of Gelée Royale, perga-pollen and pollen. Cimicifuga and Melbrosia are used through self-medication to relieve symptoms of hot flushes and other menstrual or menopausal discomfort in many of the Danish women consulting private gynaecologists. A gynaecologist tends to treat these symptoms with oestrogen, so the present experiments were therefore made to investigate whether Cimicifuga and Melbrosia have oestrogenic effects as defined by the classical biological methods: uterine growth in immature mice and vaginal cornification in ovariectomized rats., Methods: Vehicle, 6, 60 or 600 mg/kg Cimicifuga or 30, 300 or 3000 mg/kg Melbrosia was administered orally for 3 days to groups of 10 immature mice and the uterus weight measured on the fourth day. Similarly, vehicle, 6, 60, 600 mg/kg Cimicifuga or 3, 30, 300 mg/kg Melbrosia was injected subcutaneously in groups of 12 ovariectomized rats for 3 days and vaginal smears investigated for signs of cornified cells. All experiments were repeated once., Results: No signs of an oestrogenic effect connected with the preparations were found in any of the experiments., Conclusions: It can be concluded that the eventual beneficial effects on menstrual or menopausal discomfort connected with Cimicifuga and Melbrosia self-medication cannot be explained as a traditional oestrogenic effect as measured in biological experiments.