The geographical and topographical distribution of Ixodes ricinus in Finland.

Kielet ruotsi, englanti ja saksa. Helsinki 1960-1961

Pain control after total knee arthroplasty: a randomized trial comparing local infiltration anesthesia and continuous femoral block

Local infiltration analgesia (LIA) is a new multimodal wound infiltration method. It has attracted growing interest in recent years and is widely used all over the world for treating postoperative pain after knee and hip arthroplasty. This method is based on systematic infiltration of a mixture of ropivacaine, a long acting local anesthetic, ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures subject to surgical trauma inknee and hip arthroplasty. Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty (TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to the work presented in this thesis. In a randomized trial the efficacy of LIA in TKA with regard to pain at rest and upon movement was compared to femoral block. Both methods result in a high quality pain relief and similar morphine consumption, but fewer patients in the LIA group reported pain of 7/10 on any occasion during the 24 h monitoring period (paper I). In the same patient cohort the maximal total plasma concentration of ropivacaine was below the established toxic threshold for most patients although a few reached potentially toxic concentrations of 1.4-1.7 mg/L. The time to maximal detected plasma concentration was around 4-6 h after release of tourniquet in TKA (paper II). All patients in the THA cohort were subjected to the routine LIA protocol. In these patients both the total and unbound plasma concentration of ropivacaine was determined. The concentration was below the established toxic threshold. As ropivacaine binds to a-1 acid glycoprotein(AAG) we assessed the possibility that increased AAG may decrease the unbound concentration of ropivacaine. A40 % increase in AAG was detected during the first 24 h after surgery, however the fraction of unbound ropivacaine remained the same. There was a trend towards increased C max of ropivacaine with increasing age and decreasing creatinine clearance but the statistical power was too low to draw any conclusion (paper III). Administration of 30mg ketorolac according to the LIA protocol both in TKA and THA resulted in a similar Cmax as previously reported after 10 mg intramuscular ketorolac (paper II, paper IV). Neither age, nor body weight or BMI, nor creatinine clearance, correlates to maximal ketorolac plasma concentration or total exposure to ketorolac (AUC) (paper IV). In conclusion, LIA provides good postoperative analgesia which is similar to femoral block after total knee arthroplasty. The plasma concentration of ropivacaine seems to be below toxic levels in most TKA patients. The unbound plasma concentration of ropivcaine in THA seems to be below the toxic level. The use of ketorolac in LIA may not be safer than other routes of administration, and similar restrictions should be applied in patients at risk of developing side effects

Mystery of fatal 'staggering disease' unravelled: novel rustrela virus causes severe meningoencephalomyelitis in domestic cats

‘Staggering disease’ is a neurological disease entity considered a threat to European domestic cats (Felis catus) for almost five decades. However, its aetiology has remained obscure. Rustrela virus (RusV), a relative of rubella virus, has recently been shown to be associated with encephalitis in a broad range of mammalian hosts. Here, we report the detection of RusV RNA and antigen by metagenomic sequencing, RT-qPCR, in-situ hybridization and immunohistochemistry in brain tissues of 27 out of 29 cats with non-suppurative meningoencephalomyelitis and clinical signs compatible with’staggering disease’ from Sweden, Austria, and Germany, but not in non-affected control cats. Screening of possible reservoir hosts in Sweden revealed RusV infection in wood mice (Apodemus sylvaticus). Our work indicates that RusV is the long-sought cause of feline ‘staggering disease’. Given its reported broad host spectrum and considerable geographic range, RusV may be the aetiological agent of neuropathologies in further mammals, possibly even including humans

Tactile massage and hypnosis as a health promotion for nurses in emergency care-a qualitative study

<p>Abstract</p> <p>Background</p> <p>This study explores nursing personnel's experiences and perceptions of receiving tactile massage and hypnosis during a personnel health promotion project. Nursing in a short term emergency ward environment can be emotionally and physically exhausting due to the stressful work environment and the high dependency patient care. A health promotion project integrating tactile massage and hypnosis with conventional physical activities was therefore introduced for nursing personnel working in this setting at a large university hospital in Sweden.</p> <p>Methods</p> <p>Four semi-structured focus group discussions were conducted with volunteer nursing personnel participants after the health promotion project had been completed. There were 16 participants in the focus groups and there were 57 in the health promotion intervention. The discussions were transcribed verbatim and analysed with qualitative content analysis.</p> <p>Results</p> <p>The findings indicated that tactile massage and hypnosis may contribute to reduced levels of stress and pain and increase work ability for some nursing personnel. The sense of well-being obtained in relation to health promotion intervention with tactile massage and hypnosis seemed to have positive implications for both work and leisure. Self-awareness, contentment and self-control may be contributing factors related to engaging in tactile massage and hypnosis that might help nursing personnel understand their patients and colleagues and helped them deal with difficult situations that occurred during their working hours.</p> <p>Conclusion</p> <p>The findings indicate that the integration of tactile massage and hypnosis in personnel health promotion may be valuable stress management options in addition to conventional physical activities.</p

A trial to evaluate the effect of the sodium–glucose co‐transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA‐HF)

Background: Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown. Design and methods: The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF) is an international, multicentre, parallel group, randomized, double‐blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N‐terminal pro B‐type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. The trial is event‐driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient‐reported outcomes. A total of 4744 patients have been randomized. Conclusions: DAPA‐HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Leadership and Group Dynamics in Lord of the Flies and Tomorrow, When the War Began

The purpose of this essay is to compare and contrast the two novels by focusing on leadership and group dynamics. First, I explain some general terms like primary and secondary groups, leader and leadership, and five different leadership styles (autocratic, democratic, laissez-faire, task-motivated and relationship-motivated leader), and then I apply the terms to the novels. In the analysis I examine how some followers and group constellations react to different kinds of leadership, and how the three leaders choose to approach their roles and why they become successful or not. The effect the democratic leadership has on both leaders and followers differs between the novels. Homer in Tomorrow, When the War Began trusts his leadership skills and gets appreciation from the primary group of friends he leads, while Ralph in Lord of the Flies is disobeyed and challenged by his secondary group. The group of teenagers grows stronger together, while the island boys disband as a result of the power struggle between Ralph and Jack. The latter trusts his charisma and threatens and punishes the boys in order to keep them under control. Jack seems successful as an autocratic leader, since his followers carry out his orders and let him be the unquestioned leader, but he is in the final analysis unsuccessful since he fails to put the needs of his followers before his own strong desire for power. Both Homer and Jack are strong leaders of their own primary group, and one argument why they are more successful than Ralph is the loyalty they receive from their followers. However, the reason for their faithfulness differs. In Homer’s case it is friendship, and in Jack’s case it is fear of what he will do to them if they defy him

Opioids in the management of pain during delivery

OPIOIDS IN THE MANAGEMENT OF PAIN DURING DELIVERY Christina Olofsson ABSTRA CT Labour and delivery involve severe pain for most women. The goal for pain treatment in obstetrics is to provide effective and safe analgesia during all phases of delivery. The ideal method for pain relief during delivery is not yet available. This thesis aims at studying some aspects of opioids in obstetric pain treatment with respect to analgesic efficacy and side- effects, and to analyse pain during delivery from a neurobiological perspective. The analgesic effect of systemically given opioids was studied in a dose-response and in a prospective randomised and double-blind fashion. A lack of clinically significant analgesic effect was observed despite pronounced sedation. The results are interpreted to suggest that visceral pain during active labour is poorly responsive to systemically given opioids. Epidural analgesia (EDA) only using local anaesthetics is a most effective technique for pain relief during labour but is considered to increase the frequency of instrumental deliveries (vacuum extraction and Caesarean section). In a prospective, controlled randomised study in 1000 parturients during active labour, a 50% reduction of bupivacaine, but with addition of the lipophilic opioid sufentanil to sustain analgesia, the frequency of instrumental delivery was significantly reduced. The addition of sufentanil to EDA did not increase the risk of post-partum urinary retention. The anaesthetic quality during Caesarean section was studied, using a randomised and double-blind technique, in 100 parturients receiving either epidural or subarachnoidal anaesthesia with bupivacaine. In half of the patients the lipophilic opioid fentanyl was added. Intraoperative pain and discomfort did not differ significantly between the groups, indicating that an adequate dose of a local anaesthetic (bupivacaine) is of major importance when using either of the two regional anaesthetic techniques. No clinically significant effect of adding fentanyl was observed with respect to postoperative pain. The theoretical additive or synergistic effect of fentanyl, was possibly "masked" by adequate dosage of local anaesthetic. The concentration of the excitatory amino acid aspartate was significantly increased in cerebrospinal fluid during active labour but unexpectedely the concentration of nitrate (reflecting nitric oxide) was significantly lower than in controls. No effect was seen on concentrations of substance P, substance P-endopeptidase or met-enchephalin. Our results suggest that excitatory amino acids and nitric oxide are of importance in spinal nociception and visceral pain during active labour. In conclusion, we suggest that systemic opioids, still one of the most widely used methods for "analgesia" in obstetrics, should not be administered for analgesia during labour. The epidural technique can be significantly improved with respect to the frequency of instrumental deliveries by reducing the amount of local anaesthetic and by adding a lipophilic opioid. Thereby the use of epidural analgesia could be increased in order to meet the demands from parturients in pain. Anaesthetic quality during Caesarean section using regional techniques is primarily determined by the amount of local anaesthetic used. Knowledge of the mechanisms of excitatory amino acids more detailed may permit the development of new and improved pain control strategies during labour. Key words: Labour pain, systemic opioids, analgesia, epidural, subarachnoid, sufentanll, fentanyl, postpartal urinary retention, caesarean section, cerebrospinal fluld, endogenous pain controlling mechanisms STOCKHOLM 1996 ISBN 91-628-2212-