Do Lefty and Righty Matter More Than Lefty Alone?

Derek Parfit argues that fission is prudentially better for you than ordinary death. But is having more fission products with good lives prudentially better for you than having just one? In this paper, we argue that it is. We argue that, if your brain is split and the halves are transplanted into two recipients (who both have good lives), then it is prudentially better for you if both transplants succeed than if only one of them does (other things being equal). This upshot rules out, among other things, that the prudential value of standing in the relation that matters in survival to multiple people is equal to their average well-being

Kundvårdens betydelse för ridskolan

Idag minskar antalet elever på ridskolorna i Sverige. Siffror från Svenska Ridsportförbundet belyser detta. Antalet medlemmar i förbundet har minskat från cirka 202 000 år 2001 till 170 000 år 2009. Även antalet anslutna föreningar har minskat från 976 stycken år 2001 till 931 stycken år 2009 (Verksamhetsberättelse, 2001-2009). Kundvård kan vara en metod att vända på denna utveckling (personligt meddelande Nauclér). Företag har arbetat med förtroende och relationer bland människor, det underlättar och det blir mindre kostnader att servera befintliga kunder. Befintliga kunder representerar ett kontinuerligt intäktsflöde och förlorar man kunderna uppstår en störning i flödet. Det kostar mycket pengar och tar ofta lång tid att bygga upp förtroende och nya rutiner (Jakobsson, 1998). Syftet med studien är att få ökad kunskap om kundvårdens betydelse på ridskolorna i konkurrensutrett område. Detta är en av anledningarna till att vi valt Stockholms stad som undersökningsområde. I studien har vi för avsikt att kartlägga vad verksamhetsledarna anser att kundvård är, hur det historiskt har sett ut för ridskolans kundvård samt vilken betydelse kundvården kan komma att få i framtiden. Intervjun har vi kompletterat med en okulärbesiktning för att få en bild av hur kundvården fungerar i praktiken på anläggningarna. Frågeställningen för okulärbesiktningen är hur anläggningen uppfattats av en presumtiv kund. Studiens övriga frågeställningar är vad verksamhetsledarna har för syn på kundvård och vad verksamhetsledarna tror att kundvård kommer att få för betydelse i framtiden. Problemställningen är att antalet medlemmar har minskat på ridskolorna i landet. Det innebär att ridskolorna måste hitta vägar för att behålla sina nuvarande kunder och locka nya. Vi har använt en halvstrukturerad kvalitativ metod vid intervjuundersökningen och genomfört en okulärbesiktning på anläggningen. Vi har kopplat ihop intervjun med okulärbesiktningen för att kunna uppskatta dagsformen på ridskolans kundvård. Sju av åtta ridskolor i Stockholm stad deltog i vår undersökning. Samtliga drivs i privat regi och finns inom ett begränsat geografiskt område vilket gör att kunden kan välja ridskola. Verksamhetsledarna intervjuades angående begreppet kundvård samt anläggningen okulärbesiktades. Intervjuerna spelades in och all information behandlades konfidentiellt. Okulärbesiktningen genomfördes efter en rundvandring med verksamhetsledaren. Resultatet redovisas anonymt. Resultat visade bland annat att verksamhetsledarna tror att kundvården kommer bli allt viktigare i framtiden, på grund av samhällets utveckling. Vi tyckte oss kunna se ett samband mellan intervjun och okulärbesiktningen på respektive ridskola. Där verksamhetsledaren visade mindre intresse och engagemang för kundvården gav vår okulärbesiktning samma resultat till den del okulärbesiktningen handlar om den välkomnande atmosfären

Psychosocial Predictors of Drop-Out from Organised Sport: A Prospective Study in Adolescent Soccer

In recent years an increased drop-out rate in adolescents’ soccer participation has been observed. Given the potentially adverse consequences of drop-out from soccer, more information about risk factors for drop-out is warranted. In the current study, Classification and Regression Tree (CRT) analysis was used to investigate demographic and motivational factors associated with an increased risk of drop-out from adolescent soccer. The results of this study indicate that older age, experiencing less autonomy support from the coach, less intrinsic motivation, being female, and lower socioeconomic status are factors associated with an increased risk of drop-out. An interpretation of the results of this study is that coaches play a central part in creating a sports context that facilitates motivation and continued soccer participation. Based on the findings of the current study we propose that soccer clubs implement theoretically informed coach education programs to help coaches adopt autonomy-supportive coaching strategies.Psychosocial Predictors of Drop-Out from Organised Sport: A Prospective Study in Adolescent SoccerpublishedVersio

Anthracycline-Induced Cardiotoxicity: Cardiac Monitoring by Continuous Wave-Doppler Ultrasound Cardiac Output Monitoring and Correlation to Echocardiography

Background: Anthracyclines are agents with a well-known cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using real-time continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. Methods: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). Results: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (Delta T0-T4, T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (Delta T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. Conclusions: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

<p>Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.</p> <p>Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.</p> <p>Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.</p&gt

Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice

Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the WNT16 locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long Wnt16 inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of Wnt16 inactivation on cortical thickness might be caused by early developmental andor growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis, Wnt16 was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER; Wnt16(flox/flox) (Cre-Wnt16(flox/flox)) mice. First, 10-week-old Cre-Wnt16(flox/flox) and Wnt16(flox/flox) littermate control mice were treated with tamoxifen. Four weeks later, Wnt16 mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in Cre-Wnt16(flox/flox) mice compared to Wnt16(flox/flox) mice. Then, inactivation of Wnt16 in 47-week-old mice (evaluated four weeks later) resulted in a reduction of Wnt16 mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites

Prescribing indicators at primary health care centers within the WHO African region: a systematic analysis (1995-2015)

Abstract Background Rational medicine use is essential to optimize quality of healthcare delivery and resource utilization. We aim to conduct a systematic review of changes in prescribing patterns in the WHO African region and comparison with WHO indicators in two time periods 1995–2005 and 2006–2015. Methods Systematic searches were conducted in PubMed, Scopus, Web of science, Africa-Wide Nipad, Africa Journals Online (AJOL), Google scholar and International Network for Rational Use of Drugs (INRUD) Bibliography databases to identify primary studies reporting prescribing indicators at primary healthcare centres (PHCs) in Africa. This was supplemented by a manual search of retrieved references. We assessed the quality of studies using a 14-point scoring system modified from the Downs and Black checklist with inclusions of recommendations in the WHO guidelines. Results Forty-three studies conducted in 11 African countries were included in the overall analysis. These studies presented prescribing indicators based on a total 141,323 patient encounters across 572 primary care facilities. The results of prescribing indicators were determined as follows; average number of medicines prescribed per patient encounter = 3.1 (IQR 2.3–4.8), percentage of medicines prescribed by generic name =68.0 % (IQR 55.4–80.3), Percentage of encounters with antibiotic prescribed =46.8 % (IQR 33.7–62.8), percentage of encounters with injection prescribed =25.0 % (IQR 18.7–39.5) and the percentage of medicines prescribed from essential medicines list =88.0 % (IQR 76.3–94.1). Prescribing indicators were generally worse in private compared with public facilities. Analysis of prescribing across two time points 1995–2005 and 2006–2015 showed no consistent trends. Conclusions Prescribing indicators for the African region deviate significantly from the WHO reference targets. Increased collaborative efforts are urgently needed to improve medicine prescribing practices in Africa with the aim of enhancing the optimal utilization of scarce resources and averting negative health consequences

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms