Severity as a Priority Setting Criterion: Setting a Challenging Research Agenda

Priority setting in health care is ubiquitous and health authorities are increasingly recognising the need for priority setting guidelines to ensure efficient, fair, and equitable resource allocation. While cost-effectiveness concerns seem to dominate many policies, the tension between utilitarian and deontological concerns is salient to many, and various severity criteria appear to fill this gap. Severity, then, must be subjected to rigorous ethical and philosophical analysis. Here we first give a brief history of the path to today’s severity criteria in Norway and Sweden. The Scandinavian perspective on severity might be conducive to the international discussion, given its long-standing use as a priority setting criterion, despite having reached rather different conclusions so far. We then argue that severity can be viewed as a multidimensional concept, drawing on accounts of need, urgency, fairness, duty to save lives, and human dignity. Such concerns will often be relative to local mores, and the weighting placed on the various dimensions cannot be expected to be fixed. Thirdly, we present what we think are the most pertinent questions to answer about severity in order to facilitate decision making in the coming years of increased scarcity, and to further the understanding of underlying assumptions and values that go into these decisions. We conclude that severity is poorly understood, and that the topic needs substantial further inquiry; thus we hope this article may set a challenging and important research agenda

Mixed origin of juvenile Atlantic cod (Gadus morhua) along the Swedish west coast

Cryptic population structure in exploited fishes poses a major challenge for fisheries management. In Atlantic cod, sympatric ecotypes are well-known, for instance off the coast of northern Norway. Recently, two sympatric cod ecotypes have also been documented in the Skagerrak and Kattegat, where adult cod has declined dramatically. One ecotype has an apparent offshore origin and displays a more migratory lifestyle than the other, which is generally resident at the coast throughout its life. To investigate their relative abundances along the Swedish west coast, juvenile cod were collected at high spatial resolution along the coast and genetically assigned to ecotypes. The results reveal large proportions of the coastal ecotype in the southern Kattegat, Öresund, and inshore Swedish Skagerrak, whereas the offshore ecotype dominates in offshore areas. A regression model comparison suggests that differences in bottom depth, rather than distance from the open sea, explain the heterogeneous spatial distribution of the two ecotypes. In addition, the two ecotypes display genetic differences suggesting adaptation to different environments. The results underline that successful fisheries management requires identification and consideration of locally adapted sympatric ecotypes.publishedVersio

Mixed origin of juvenile Atlantic cod (Gadus morhua) along the Swedish west coast

Cryptic population structure in exploited fishes poses a major challenge for fisheries management. In Atlantic cod, sympatric ecotypes are well-known, for instance off the coast of northern Norway. Recently, two sympatric cod ecotypes have also been documented in the Skagerrak and Kattegat, where adult cod has declined dramatically. One ecotype has an apparent offshore origin and displays a more migratory lifestyle than the other, which is generally resident at the coast throughout its life. To investigate their relative abundances along the Swedish west coast, juvenile cod were collected at high spatial resolution along the coast and genetically assigned to ecotypes. The results reveal large proportions of the coastal ecotype in the southern Kattegat, Öresund, and inshore Swedish Skagerrak, whereas the offshore ecotype dominates in offshore areas. A regression model comparison suggests that differences in bottom depth, rather than distance from the open sea, explain the heterogeneous spatial distribution of the two ecotypes. In addition, the two ecotypes display genetic differences suggesting adaptation to different environments. The results underline that successful fisheries management requires identification and consideration of locally adapted sympatric ecotypes.publishedVersionPaid open acces

Elevated atrial blood stasis in paroxysmal atrial fibrillation during sinus rhythm: a patient-specific computational fluid dynamics study

IntroductionAtrial fibrillation (AF) is associated with an increased risk of stroke, often caused by thrombi that form in the left atrium (LA), and especially in the left atrial appendage (LAA). The underlying mechanism is not fully understood but is thought to be related to stagnant blood flow, which might be present despite sinus rhythm. However, measuring blood flow and stasis in the LAA is challenging due to its small size and low velocities. We aimed to compare the blood flow and stasis in the left atrium of paroxysmal AF patients with controls using computational fluid dynamics (CFD) simulations.MethodsThe CFD simulations were based on time-resolved computed tomography including the patient-specific cardiac motion. The pipeline allowed for analysis of 21 patients with paroxysmal AF and 8 controls. Stasis was estimated by computing the blood residence time.Results and DiscussionResidence time was elevated in the AF group (p < 0.001). Linear regression analysis revealed that stasis was strongest associated with LA ejection ratio (p < 0.001, R2 = 0.68) and the ratio of LA volume and left ventricular stroke volume (p < 0.001, R2 = 0.81). Stroke risk due to LA thrombi could already be elevated in AF patients during sinus rhythm. In the future, patient specific CFD simulations may add to the assessment of this risk and support diagnosis and treatment

LRIG1 negatively regulates RET mutants and is downregulated in thyroid cancer

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-Type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.Fil: Lindquist, David. Universidad de Umea; SueciaFil: Alsina, Fernando Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Herdenberg, Carl. Universidad de Umea; SueciaFil: Larsson, Catharina. Karolinska University Hospital;Fil: Höppener, Jo. University Medical Center Utrecht;Fil: Wang, Na. Karolinska University Hospital;Fil: Paratcha, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Tarján, Miklós. Falu Lasarett; SueciaFil: Tot, Tibor. Falu Lasarett; SueciaFil: Henriksson, Roger. Universidad de Umea; SueciaFil: Hedman, Håkan. Universidad de Umea; Sueci

Delivering and participating in a psycho- educational intervention for family caregivers during palliative home care: a qualitative study from the perspectives of health professionals and family caregivers

Abstract Background: Family caregivers in palliative care have a need for knowledge and support from health professionals, resulting in the need for educational and supportive interventions. However, research has mainly focused on the experiences of family caregivers taking part in interventions. To gain an increased understanding of complex interventions, it is necessary to integrate the perspectives of health professionals and family caregivers. Hence, the aim of this study is to explore the perspectives of health professionals and family caregivers of delivering and participating in a psycho-educational intervention in palliative home care. Methods: A psycho-educational intervention was designed for family caregivers based on a theoretical framework describing family caregiver's need for knowing, being and doing. The intervention was delivered over three sessions, each of which included a presentation by healthcare professionals from an intervention manual. An interpretive descriptive design was chosen and data were collected through focus group discussions with health professionals and individual interviews with family caregivers. Data were analysed using framework analysis

Registered varieties and Organic Heterogeneous Material (OHM) with resistance to common bunt in Europe

Presenting commercially available wheat varieties with resistance to common bunt

Evolving Perspectives of Stewardship in the Seafood Industry

Humanity has never benefited more from the ocean as a source of food, livelihoods, and well-being, yet on a global scale this has been accompanied by trajectories of degradation and persistent inequity. Awareness of this has spurred policymakers to develop an expanding network of ocean governance instruments, catalyzed civil society pressure on the public and private sector, and motivated engagement by the general public as consumers and constituents. Among local communities, diverse examples of stewardship have rested on the foundation of care, knowledge and agency. But does an analog for stewardship exist in the context of globally active multinational corporations? Here, we consider the seafood industry and its efforts to navigate this new reality through private governance. We examine paradigmatic events in the history of the sustainable seafood movement, from seafood boycotts in the 1970s through to the emergence of certification measures, benchmarks, and diverse voluntary environmental programs. We note four dimensions of stewardship in which efforts by actors within the seafood industry have aligned with theoretical concepts of stewardship, which we describe as (1) moving beyond compliance, (2) taking a systems perspective, (3) living with uncertainty, and (4) understanding humans as embedded elements of the biosphere. In conclusion, we identify emerging stewardship challenges for the seafood industry and suggest the urgent need to embrace a broader notion of ocean stewardship that extends beyond seafood

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Role of Physical Activity and Fitness in the Characterization and Prognosis of the Metabolically Healthy Obesity Phenotype: a Systematic Review and Meta-Analysis

The aims of the present article are to systematically review and meta-analyze the existing evidence on: 1) differences in physical activity (PA), sedentary behavior (SB), cardiorespiratory fitness (CRF) and muscular strength (MST) between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO); and 2) the prognosis of all-cause mortality and cardiovascular disease (CVD) mortality/morbidity in MHO individuals, compared with the best scenario possible, i.e., metabolically healthy normal-weight (MHNW), after adjusting for PA, SB, CRF or MST. Our systematic review identified 67 cross-sectional studies to address aim 1, and 11 longitudinal studies to address aim 2. The major findings and conclusions from the current meta-analysis are: 1) MHO individuals are more active, spend less time in SB, and have a higher level of CRF (yet no differences in MST) than MUO individuals, suggesting that their healthier metabolic profile could be at least partially due to these healthier lifestyle factors and attributes. 2) The meta-analysis of cohort studies which accounted for PA (N = 10 unique cohorts, 100% scored as high-quality) support the notion that MHO individuals have a 24-33% higher risk of all-cause mortality and CVD mortality/morbidity compared to MHNW individuals. This risk was borderline significant/non-significant, independent of the length of the follow-up and lower than that reported in previous meta-analyses in this topic including all type of studies, which could be indicating a modest reduction in the risk estimates as a consequence of accounting for PA. 3) Only one study has examined the role of CRF in the prognosis of MHO individuals. This study suggests that the differences in the risk of all-cause mortality and CVD mortality/morbidity between MHO and MHNW are largely explained by differences in CRF between these two phenotypes