The two-year impact of first generation protease inhibitor based antiretroviral therapy (PI-ART) on health-related quality of life

BACKGROUND: Protease inhibitor based antiretroviral therapy (PI-ART) was introduced in 1996 and has greatly reduced the incidence of HIV-related morbidity and mortality in the industrialised world. PI-ART would thus be expected to have a positive effect on health-related quality of life (HRQL). On the other hand, HRQL might be negatively affected by strict adherence requirements as well as by short and long-term adverse effects. The aim of this study was to assess the influence of two years of first generation PI-ART on HRQL in patients with a relatively advanced state of HIV-infection. Furthermore, we wanted to investigate the relation between developments in HRQL and viral response, self-reported adherence and subjective experience of adverse effects in patients with PI-ART. METHODS: HRQL was measured by the Swedish Health-Related Quality of Life Questionnaire (SWED-QUAL). Sixty-three items from the SWED-QUAL forms two single-item and 11 multi-item dimension scales. For this study, two summary SWED-QUAL scores (physical HRQL composite score and emotional HRQL composite score) were created through a data reduction procedure. At the 2-year follow-up measurement (see below), items were added to measure adherence and subjective experience of adverse effects. Demographic and medical data were obtained from specific items in the questionnaires and from the medical files. Seventy-two patients who were among the first to receive PI-ART (indinavir or ritonavir based) responded to the questionnaire before the start of PI-ART. Of these, 54 responded to the same instrument after two years of treatment (13 had died, four had changed clinic and one did not receive the questionnaire). RESULTS: The main findings were that the emotional HRQL deteriorated during two years of PI-ART, while the physical HRQL remained stable. Multiple linear regression analyses showed that experience of adverse effects contributed most to the deterioration of emotional HRQL. CONCLUSION: In this sample of patients with relatively advanced state of HIV-infection, our data suggested that a negative development of physical HRQL had been interrupted by the treatment and that the emotional dimension of HRQL deteriorated during two years after start of PI-ART. Subjective experience of adverse effects made a major contribution to the decrease in emotional HRQL. The results underline the importance of including HRQL measures in the evaluation of new life prolonging therapies

Peak Bone Mass and Quantitative Ultrasound Bone Properties in Young Adulthood : A Study in the PEAK-25 Cohort of Women

Peak bone mass is normally reached in the third decade of life. Previously, in the population-based PEAK-25 cohort (n = 1061, age 25.5 ± 0.2), we demonstrated that bone mineral density in the population-based PEAK-25 cohort is comparatively high; therefore, this study aimed to determine if the calcaneus microarchitecture mirrored this. In the process, we describe normative quantitative ultrasound (QUS) values for 25-yr-old women and the relationship between QUS values and extremes of body weight. QUS variables speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index were measured. Young adult values were based on the manufacturer-supplied QUS reference values. Analyses were performed in the cohort as a whole, and additionally, to understand the relationship between body weight and QUS values in young women, the variables were categorized into octiles for weight or body mass index (BMI) and the lowest and highest octiles were compared. In the cohort, SOS values, reflecting bone density, were higher (108 ± 18%), whereas BUA values, reflecting bone complexity, were lower (90 ± 14%) compared to the young adult reference population. SOS did not correlate with body weight or BMI. In the cohort, overall correlations between BUA weight, and BMI were small and positive (Pearson's r coefficients 0.261 and 0.197, respectively; p <0.001), although in the low-weight group, r coefficients were higher (r = 0.313 and 0.268; p <0.05). In contrast, in the high-weight group, correlation with BUA values tended to be small, negative, and nonsignificant. Correlation between QUS and dual-energy X-ray absorptiometry-measured bone mineral density was low to moderate and significant at all skeletal sites (r = 0.37-0.52). Whereas coefficients tended to be higher in the low-weight group, the reverse was apparent for the low-BMI group. In these 25-yr-old women, a comparatively high dual-energy X-ray absorptiometry-measured bone mass is offset by less complex bone structures assessed by QUS. This may have implications for later osteoporosis assessment and future fracture risk

Palaeobiology, ecology, and distribution of stromatoporoid faunas in biostromes of the mid-Ludlow of Gotland

Six well exposed mid−Ludlow stromatoporoid−dominated reef biostromes in four localities from the Hemse Group in southeastern Gotland, Sweden comprise a stromatoporoid assemblage dominated by four species; Clathrodictyon mohicanum, “Stromatopora” bekkeri, Plectostroma scaniense, and Lophiostroma schmidtii. All biostromes investigated in this area (of approximately 30 km2) are interpreted to belong to a single faunal assemblage forming a dense accumulation of fossils that is probably the best exposed stromatoporoid−rich deposit of the Silurian. The results from this comprehensive study strengthen earlier interpretations of a combination of genetic and environmental control on growth−forms of the stromatoporoids. Growth styles are similar for stromatoporoids in all six biostromes. Differences in biostrome fabric are due to variations in the degree of disturbance by storms. The uniformity of facies and the widespread low−diversity fauna support the view that palaeoenvironmental conditions were similar across the area where these biostromes crop out, and promoted the extraordinary growth of stromatoporoids in this shallow shelf area

Phase-Controlled Force and Magnetization Oscillations in Superconducting Ballistic Nanowires

The emergence of superconductivity-induced phase-controlled forces in the (0.01-0.1) nN range, and of magnetization oscillations, in nanowire junctions, is discussed. A giant magnetic response to applied weak magnetic fields, is predicted in the ballistic Josephson junction formed by a superconducting tip and a surface, bridged by a normal metal nanowire where Andreev states form.Comment: 5 pages, 3 figure

Pre-hospital advanced airway management by anaesthetist and nurse anaesthetist critical care teams: a prospective observational study of 2028 pre-hospital tracheal intubations

Background: Pre-hospital tracheal intubation success and complication rates vary considerably among provider categories. The purpose of this study was to estimate the success and complication rates of pre-hospital tracheal intubation performed by physician anaesthetist or nurse anaesthetist pre-hospital critical care teams. Methods: Data were prospectively collected from critical care teams staffed with a physician anaesthetist or a nurse anaesthetist according to the Utstein template for pre-hospital advanced airway management. The patients served by six ambulance helicopters and six rapid response vehicles in Denmark, Finland, Norway, and Sweden from May 2015 to November 2016 were included. Results: The critical care teams attended to 32 007 patients; 2028 (6.3%) required pre-hospital tracheal intubation. The overall success rate of pre-hospital tracheal intubation was 98.7% with a median intubation time of 25 s and an on-scene time of 25 min. The majority (67.0%) of the patients' tracheas were intubated by providers who had performed >2500 tracheal intubations. The success rate of tracheal intubation on the first attempt was 84.5%, and 95.9% of intubations were completed after two attempts. Complications related to pre-hospital tracheal intubation were recorded in 10.9% of the patients. Intubations after rapid sequence induction had a higher success rate compared with intubations without rapid sequence induction (99.4% vs 98.1%; P=0.02). Physicians had a higher tracheal intubation success rate than nurses (99.0% vs 97.6%; P=0.03). Conclusions: When performed by experienced physician anaesthetists and nurse anaesthetists, pre-hospital tracheal intubation was completed rapidly with high success rates and a low incidence of complications.Peer reviewe

Persistent current in a one-dimensional ring of fractionally charged "exclusons''

The Aharonov-Bohm effect in a one-dimensional (1D) ring containing a gas of fractionally charged excitations is considered. It is shown that the low temperature behavior of the system is identical to that of free electrons with (integer) charge $e$. This is a direct consequence of the fact that the total charge in the ring is quantized in units of the electron charge. Anomalous oscillations of the persistent current amplitude with temperature are predicted to occur as a direct manifistation of the fractional nature of the quasiparticle charge. A 1D conducting ring with gate induced periodical potential is discussed as a possible set-up for an experimental observation of the predicted phenomenon.Comment: 4 pages, RevTex, uuencoded figure

Cell type-specific expression and localization of cytochrome P450 isoforms in tridimensional aggregating rat brain cell cultures.

Within the Predict-IV FP7 project a strategy for measurement of in vitro biokinetics was developed, requiring the characterization of the cellular model used, especially regarding biotransformation, which frequently depends on cytochrome P450 (CYP) activity. The extrahepatic in situ CYP-mediated metabolism is especially relevant in target organ toxicity. In this study, the constitutive mRNA levels and protein localization of different CYP isoforms were investigated in 3D aggregating brain cell cultures. CYP1A1, CYP2B1/B2, CYP2D2/4, CYP2E1 and CYP3A were expressed; CYP1A1 and 2B1 represented almost 80% of the total mRNA content. Double-immunolabeling revealed their presence in astrocytes, in neurons, and to a minor extent in oligodendrocytes, confirming the cell-specific localization of CYPs in the brain. These results together with the recently reported formation of an amiodarone metabolite following repeated exposure suggest that this cell culture system possesses some metabolic potential, most likely contributing to its high performance in neurotoxicological studies and support the use of this model in studying brain neurotoxicity involving mechanisms of toxication/detoxication

High prevalence of ST-elevation, early repolarization, and left ventricular hypertrophy during the eligibility assessment for an HIV vaccine trial in young, healthy Tanzanians

BACKGROUND: Vaccinia based immunizations have caused myo/pericarditis and vaccine study volunteers are monitored by ECG. We report ECG outcome obtained during the screening period for an HIV vaccine trial. METHODS: ECG was performed in healthy Tanzanian volunteers. ECG abnormalities and findings interfering with the interpretation of myo/pericarditis were subject to study ineligibility. We determined the prevalence of left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon (SL) or the Cornell index, ST-elevations and early repolarization (ERP) in association with gender, age, BMI and body height by regression analysis adjusted for gender and age. RESULTS: In 257 volunteers (median age 23 years, 63% males) overall positivity for LVH defined by SL or Cornell criteria was seen in 20.6% and 3.5%, ST-elevations ≥ 0.1 mV or ≥ 0.2 mV in 77.8% and 38.1%, and ERP in 23.4%. Positive SL criteria were associated with male gender (PR 7.84, p < 0.001) and lower age (PR 0.70, p = 0.002), and associated with increased body height and lower BMI in univariate analysis. Positive Cornell criteria were only associated with lower age (PR 0.44, p = 0.010). ST-elevations ≥ 0.2 mV were associated with male gender (PR 8.05, p < 0.001) and lower age (PR 0.81, p = 0.003), and ERP with male gender (PR 2.86, p < 0.001). Vaccine study ineligibility due to ECG findings was concluded in 22.1% of the screening population. CONCLUSIONS: High prevalence of LVH according to SL in association with ST-elevation and ERP is especially found in young and male Africans. ECG variations need to be considered for eligibility criteria in studies investigating potential cardiotoxic agents in Africa

Learning how to understand complexity and deal with sustainability challenges : A framework for a comprehensive approach and its application in university education

Sustainability challenges such as climate change, biodiversity loss, poverty and rapid urbanization are complex and strongly interrelated. In order to successfully deal with these challenges, we need comprehensive approaches that integrate knowledge from multiple disciplines and perspectives and emphasize interconnections. In short, they aid in observing matters in a wider perspective without losing an understanding of the details. In order to teach and learn a comprehensive approach, we need to better understand what comprehensive thinking actually is. In this paper, we present a conceptual framework for a comprehensive approach, termed the GHH framework. The framework comprises three dimensions: generalism, holism, and holarchism. It contributes to the academic community's understanding of comprehensive thinking and it can be used for integrating comprehensive thinking into education. Also, practical examples of the application of the framework in university teaching are presented. We argue that an ideal approach to sustainability challenges and complexity in general is a balanced, dialectical combination of comprehensive and differentiative approaches. The current dominance of specialization, or the differentiative approach, in university education calls for a stronger emphasis on comprehensive thinking skills. Comprehensiveness should not be considered as a flawed approach, but should instead be considered as important an aspect in education as specialized and differentiative skills. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe