The responsiveness of the uterine fibroid symptom and health-related quality of life questionnaire (UFS-QOL)

Abstract Background A number of noninvasive alternatives to hysterectomy have become available as treatments for uterine fibroids. These alternative therapies, however, may not relieve all symptoms. Consequently, the need for patient-reported outcomes to assess symptom reduction of uterine fibroids has become increasingly important to evaluate the clinical success of patients who choose these alternative therapies. The purpose of the study was to examine the responsiveness of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) with treatment of uterine fibroids. Methods The responsiveness of the UFS-QOL was assessed as a post-hoc analysis of patients treated with MRI-guided focused ultrasound thermal ablation (MRgFUS) for uterine fibroids. The UFS-QOL and SF-36 were completed at baseline and months 1, 3, and 6. Patient perceived overall treatment effect (OTE) was assessed at month 3, while satisfaction with treatment was collected at month 6. The responsiveness of the UFS-QOL was examined using effect sizes and change scores by patient-reported overall treatment effect and satisfaction. Results A total of 102 women with complete UFS-QOL data were included in the analysis; the mean age was 45 years and 79% were Caucasian. From baseline to 6 months, significant improvements were observed in UFS-QOL Symptom Severity and all Health-Related Quality of Life (HRQL) subscale scores (p Conclusion The UFS-QOL is responsive to treatment for uterine fibroids and is a useful outcome measure for uterine-sparing uterine fibroid treatments.</p

The use of personal response systems to renegotiate the didactical contract in tertiary mathematics education

Challenges experienced by first-year students transitioning from secondary to tertiary mathematics education are examined through the lens of the didactical contract. The didactical contract describes the expectations of both lecturer and students about their mutual obligations towards teaching and learning. First-year students’ beliefs about the nature of mathematics and mathematics teaching/learning need to be challenged to renegotiate the didactical contract at tertiary level. The study focuses on how to elicit and confront transitioning students’ beliefs in order to support their learning and influence a shift in the didactical contract. A Likert scale questionnaire was deployed at the beginning of students’ first year to gauge their beliefs about mathematics and mathematics teaching/learning and redeployed near the end of the first semester (or term) to observe possible changes in their beliefs and hence the didactical contract. The intervention consisted of personal response system (PRS) sessions regularly incorporated into the traditional transmission mode lecture to flip the classroom and create a student-centred learning environment, aimed at influencing students’ beliefs in order to make them aware of their own learning and their responsibility for learning. Questionnaire data were quantified and compared for the before and after surveys. There is evidence of a shift towards students taking ownership of their learning and a renegotiation of the didactical contract. Qualitative data generated by focus group interviews confirm the role of the PRS sessions in influencing student beliefs and the didactical contract.https://journals.co.za/journal/newgenam2023Science, Mathematics and Technology Educatio

Seasonal Activity Budget of Adult Baltic Ringed Seals

Although ringed seals are important components in oceanic and fresh water ecosystems at high latitudes, little is known about how they exploit these harsh environments. Seasonal activity and diving behaviour of 19 adult Baltic ringed seals were studied by satellite telemetry. We elaborated an activity budget for ten months of the year, extending over the period from moult to the breeding season. Seals from three main regions showed explicit site fidelity and the distributions of animals tagged from different areas did not overlap, suggesting separate stocks. Both the mean duration and the mean depth of dives peaked in June and July. Seals spent 70% (females) to 85% (males) of their time diving in June and July which decreased to 50% in late autumn. Less than one percent of dives exceeded 10 min in females, while 10% of male dives lasted longer than 10 min in June to September. Less than one percent of dives lasted for more than 25 min. Both females and males were most active during day time and hauled out predominantly during the night. Activity patterns during the summer are suggested to be correlated to energy accumulation and prey availability. The information on seasonal activity budget is crucial for developing population energetic models where interactions between ringed seals and other trophic levels can be evaluated

Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals

Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1–3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations

Phylogenomic insights to the origin and spread of phocine distemper virus in European harbour seals in 1988 and 2002

The study was supported by the Villum Foundation, the Danish Ministry of the Environment, the Volkswagen Foundation (Az.: 89911) and the BONUS programme BaltHealth, which has received funding from BONUS (Art. 185), funded jointly by the EU, Innovation Fund Denmark (grants 6180-00001B and 6180-00002B), Forschungszentrum Jülich GmbH, German Federal Ministry of Education and Research (grant FKZ 03F0767A), Academy of Finland (grant 311966) and Swedish Foundation for Strategic Environmental Research (MISTRA).The 1988 and 2002 phocine distemper virus (PDV) outbreaks in European harbour seals Phoca vitulina are among the largest mass mortality events recorded in marine mammals. Despite its large impact on harbour seal population numbers, and 3 decades of studies, many questions regarding the spread and temporal origin of PDV remain unanswered. Here, we sequenced and analysed 7123 bp of the PDV genome, including the coding and non-coding regions of the entire P, M, F and H genes in tissues from 44 harbour seals to shed new light on the origin and spread of PDV in 1988 and 2002. The phylogenetic analyses trace the origin of the PDV strain causing the 1988 outbreak to between June 1987 and April 1988, while the origin of the strain causing the 2002 outbreak can be traced back to between July 2001 and April 2002. The analyses further point to several independent introductions of PDV in 1988, possibly linked to a southward mass immigration of harp seals in the winter and spring of 1987−1988. The vector for the 2002 outbreak is unknown, but the epidemiological analyses suggest the subsequent spread of PDV from the epicentre in the Kattegat, Denmark, to haul-out sites in the North Sea through several independent introductions.PostprintPeer reviewe

Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in patients with a previous myocardial infarction:a randomised controlled trial

OBJECTIVE: The mechanisms through which ω-3 fatty acids reduce adverse cardiac events remain uncertain. We aimed to investigate the effect of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis, and platelet and monocyte activation in patients with coronary heart disease. DESIGN: Randomised, double-blind, placebo-controlled, cross-over trial. SETTING: Academic cardiac centre. PARTICIPANTS: 20 male patients with a previous myocardial infarction. INTERVENTION: ω-3 Fatty acid supplementation (2 g/day for 6 weeks) versus olive oil placebo. OUTCOME MEASURES: Peripheral blood was taken for analysis of platelet and monocyte activation, and forearm blood flow (FBF) was assessed in a subset of 12 patients during intrabrachial infusions of acetylcholine, substance P and sodium nitroprusside. Stimulated plasma tissue plasminogen activator (t-PA) concentrations were measured during substance P infusion. RESULTS: All vasodilators caused dose-dependent increases in FBF (p<0.0001). ω-3 Fatty acid supplementation did not affect endothelium-dependent vasodilation with acetylcholine and substance P compared with placebo (p=0.5 and 0.9). Substance P caused a dose-dependent increase in plasma t-PA concentrations (p<0.0001), which was not affected by ω-3 fatty acid supplementation (p=0.9). ω-3 Fatty acids did not affect platelet–monocyte aggregation, platelet P-selectin or CD40L, or monocyte CD40. CONCLUSIONS: We have demonstrated that dietary supplementation with ω-3 fatty acids does not affect endothelial vasomotor function, endothelial t-PA release, or platelet and monocyte activation in patients with coronary heart disease. Cardiac benefits conferred by ω-3 fatty acids in coronary heart disease are unlikely to be mediated through effects on these systems

JNK interacting protein 1 (JIP-1) protects LNCaP prostate cancer cells from growth arrest and apoptosis mediated by 12-0-tetradecanoylphorbol-13-acetate (TPA)

12-0-tetradecanoylphorbol-13-acetate (TPA) stimulates protein kinase C (PKC) which mediates apoptosis in androgen-sensitive LNCaP human prostate cancer cells. The downstream signals of PKC that mediate TPA-induced apoptosis in LNCaP cells are unclear. In this study, we found that TPA activates the c-Jun NH2-terminal kinase (JNK)/c-Jun/AP-1 pathway. To explore the possible role that the JNK/c-Jun/AP-1 signal pathway has on TPA-induced apoptosis in LNCaP cells, we stably transfected the scaffold protein, JNK interacting protein 1 (JIP-1), which binds to JNK inhibiting its ability to phosphorylate c-Jun. TPA (10(-9)-10(-7) mol l(-1)) caused phosphorylation of JNK in both wild-type and JIP-1-transfected (LNCaP-JIP-1) cells. It resulted in phosphorylation and upregulation of expression of c-Jun protein in the wild-type LNCaP cells, but not in the JIP-1-transfected LNCaP cells. In addition, upregulation of AP-1 reporter activity by TPA (10(-9) mol l(-1)) occurred in LNCaP cells but was abrogated in LNCaP-JIP-1 cells. Thus, TPA stimulated c-Jun through JNK, and JIP-1 effectively blocked JNK. TPA (10(-12)-10(-8) mol l(-1)) treatment of LNCaP cells caused their growth inhibition, cell cycle arrest, upregulation of p53 and p21waf1, and induction of apoptosis. All of these effects were significantly attenuated when LNCaP-JIP-1 cells were similarly treated with TPA. A previous study showed that c-Jun/AP-1 blocked androgen receptor (AR) signaling by inhibiting AR binding to AR response elements (AREs) of target genes including prostate-specific antigen (PSA). Therefore, we hypothesised that TPA would not be able to disrupt the AR signal pathway in LNCaP-JIP-1 cells. Contrary to expectation, TPA (10(-9)-10(-8) mol l(-1)) inhibited DHT-induced AREs reporter activity and decreased levels of PSA in the LNCaP-JIP-1 cells. Taken together, TPA, probably by stimulation of PKC, phosphorylates JNK, which phosphorylates and increases expression of c-Jun leading to AP-1 activity. Growth control of prostate cancer cells can be mediated through the JNK/c-Jun pathway, but androgen responsiveness of these cells can be independent of this pathway, suggesting that androgen independence in progressive prostate cancer may not occur through activation of this pathway

The unfolded protein response governs integrity of the haematopoietic stem-cell pool during stress.

The blood system is sustained by a pool of haematopoietic stem cells (HSCs) that are long-lived due to their capacity for self-renewal. A consequence of longevity is exposure to stress stimuli including reactive oxygen species (ROS), nutrient fluctuation and DNA damage. Damage that occurs within stressed HSCs must be tightly controlled to prevent either loss of function or the clonal persistence of oncogenic mutations that increase the risk of leukaemogenesis. Despite the importance of maintaining cell integrity throughout life, how the HSC pool achieves this and how individual HSCs respond to stress remain poorly understood. Many sources of stress cause misfolded protein accumulation in the endoplasmic reticulum (ER), and subsequent activation of the unfolded protein response (UPR) enables the cell to either resolve stress or initiate apoptosis. Here we show that human HSCs are predisposed to apoptosis through strong activation of the PERK branch of the UPR after ER stress, whereas closely related progenitors exhibit an adaptive response leading to their survival. Enhanced ER protein folding by overexpression of the co-chaperone ERDJ4 (also called DNAJB9) increases HSC repopulation capacity in xenograft assays, linking the UPR to HSC function. Because the UPR is a focal point where different sources of stress converge, our study provides a framework for understanding how stress signalling is coordinated within tissue hierarchies and integrated with stemness. Broadly, these findings reveal that the HSC pool maintains clonal integrity by clearance of individual HSCs after stress to prevent propagation of damaged stem cells

Experimental Aspects of Synthesis

We discuss the problem of experimentally evaluating linear-time temporal logic (LTL) synthesis tools for reactive systems. We first survey previous such work for the currently publicly available synthesis tools, and then draw conclusions by deriving useful schemes for future such evaluations. In particular, we explain why previous tools have incompatible scopes and semantics and provide a framework that reduces the impact of this problem for future experimental comparisons of such tools. Furthermore, we discuss which difficulties the complex workflows that begin to appear in modern synthesis tools induce on experimental evaluations and give answers to the question how convincing such evaluations can still be performed in such a setting.Comment: In Proceedings iWIGP 2011, arXiv:1102.374