Den anden som belastning - om reproduktiv kloning

Artiklen tager udgangspunkt i at den modstand mod reproduktiv kloning, der hidtil har gjort sig gældende, ikke mere er selvfølgelig. Provokeret heraf fremsættes et etisk argument imod reproduktiv kloning, der er begrundet i det forhold, at mennesket ifølge Schmidt og Holm tilhører ’forskellen til den anden’. Som en lokal manifestation af den ’pragmatiske fejlslutning’, der karakteriserer udviklingen af den moderne medicin, nemlig at enhver ’kunnen’ nødvendigvis artikulerer sig i en ’skullen’, er kloning således forbundet med en overskridelse af det incestforbud, der som grænsemarkering fungerer som et væsentligt fundament for vores kultur. Schmidt og Holm redegør nemlig for, hvordan reproduktiv kloning kan betragtes som udtryk for en ultimativ narcissisme, idet den karakteriserer et menneskeligt ønske om at overskride døden og blive identisk med sig selv

Mortality Risk Among Heart Failure Patients With Depression:A Nationwide Population-Based Cohort Study

BACKGROUND: The prevalence of depression is 4‐ to 5‐fold higher in heart failure patients than in the general population. We examined the influence of depression on all‐cause mortality in patients with heart failure. METHODS AND RESULTS: Using Danish medical registries, this nationwide population‐based cohort study included all patients with a first‐time hospitalization for heart failure (1995–2014). All‐cause mortality risks and 19‐year mortality rate ratios were estimated based on Cox regression analysis, adjusting for age, sex, time period, comorbidity, and socioeconomic status. The analysis included 9636 patients with and 194 887 patients without a diagnosis of depression. Compared with patients without a history of depression, those with depression had higher 1‐year (36% versus 33%) and 5‐year (68% versus 63%) mortality risks. Overall, the adjusted mortality rate ratio was 1.03 (95% CI 1.01–1.06). Compared with no depression, the adjusted mortality rate ratios for mild, moderate, and severe depression, as defined by diagnostic codes, were 1.06 (95% CI 1.00–1.13), 1.03 (95% CI 0.99–1.08), and 1.02 (95% CI 0.96–1.09), respectively. In a subcohort of patients, the mortality rate ratios were modified by left ventricular ejection fraction, with adjusted mortality rate ratios of 1.17 (95% CI, 1.05–1.31) for ≤35%, 0.98 (95% CI 0.81–1.18) for 36% to 49%, and 0.96 (95% CI 0.74–1.25) for ≥50%. Results were consistent after adjustment for alcohol abuse and smoking. CONCLUSIONS: A history of depression was an adverse prognostic factor for all‐cause mortality in heart failure patients with left ventricular ejection fraction ≤35% but not for other heart failure patients

The Western Denmark Cardiac Computed Tomography Registry:a review and validation study

BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We examined the content, data quality, and research potential of the WDHR-CCTR. METHODS: We retrieved 2008–2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. RESULTS: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%–100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%). CONCLUSION: WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research

SHELTERFISH New tools to improve fish health and environment in organic aquaculture

Rainbow trout farming and in particular organic rainbow trout farms are critically challenged by the relatively high prevalence of skin/gill infections caused by various pathogens, especially the parasite Costia (Ichthyobodo necator) and amoebae, which are ultimately lethal for fry/smaller fish. In addition, a Midichloria-like bacterium causes the non-lethal skin disease Red Mark Syndrome (RMS), which results in downgrading/rejection of up to 30% of the fish when placed on the market. Treatment by use of antibiotics/parasitics/ auxiliary compounds is only possible to a limited extent in organic trout production. Hence, solutions to prevent and/or treat costia, amoebae and RMS are urgently needed, not only to secure production of organic rainbow trout in Denmark, but also enable a larger and more cost efficient production with high animal welfare and minimal environmental impact. ShelterFish will focus on solutions addressing the interactions between fish - pathogens – farming environment and water quality; including 1) Test of artificial shelters (shade) to enrich environmental conditions and lower stress; 2) Test of biological herb extracts and a new bacterial surfactant to minimize gill/skin parasite infections; 3) Test of induced immunity to Red Mark Syndrome (RMS) by early exposure; and 4) Test of tools to reduce organic matter load in organic trout farms and hereby improve water quality, fish health/welfare

Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and β1

Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the epidermis, is maintained in suprabasal keratinocytes in psoriatic skin, modulating proliferation and differentiation as well as leukocyte infiltration. Here, we generated minipigs co-expressing integrins α2 and β1 in suprabasal epidermal layers. Integrin-transgenic minipigs born into the project displayed skin phenotypes that correlated with the number of inserted transgenes. Molecular analyses were in good concordance with histological observations of psoriatic hallmarks, including hypogranulosis and T-lymphocyte infiltration. These findings mark the first creation of minipigs with a psoriasiform phenotype resembling human psoriasis and demonstrate that integrin signaling plays a key role in psoriasis pathology

Comparison of efficacy in patients with metastatic melanoma treated with ipilimumab and nivolumab who did or did not discontinue treatment due to immune-related adverse events:A real-world data study

SIMPLE SUMMARY: This retrospective study of real-world patients with metastatic melanoma shows that discontinuing treatment with combination immunotherapy due to adverse events does not result in a poorer outcome compared to patients that did not discontinue due to toxicity. This is important knowledge for clinicians and patients, as discontinuing treatment may cause great anxiety for patients because they believe that it may limit the response. ABSTRACT: Immune-related adverse events (irAEs) are very prevalent when treating patients with ipilimumab and nivolumab in combination, and 30–40% of patients discontinue the treatment for this reason. It is of high clinical relevance to investigate the consequences of discontinuing the treatment early since combination therapy with ipilimumab and nivolumab is the first line of treatment for many patients with metastatic melanoma. In this follow-up study, with real-world data from the nationwide DAMMED database, we investigated whether there was a difference in progression-free survival (PFS) and overall survival (OS) for patients who discontinued or did not discontinue treatment within the first four doses of treatment due to irAEs. In total, 448 patients were treated with ipilimumab and nivolumab. Of these, 133 patients discontinued due to irAEs in the induction phase. Using the Cox proportional hazards model, there was no significant difference in PFS when comparing the group that discontinued with the group that did not discontinue. The group that discontinued had a significantly longer OS than the group that received the full length of treatment. Therefore, we conclude that there is no significant negative impact on efficacy for patients who discontinue due to irAEs in the induction phase of combination immunotherapy for metastatic melanoma