Completeness and validity in a national clinical thyroid cancer database: DATHYRCA

BackgroundAlthough a prospective national clinical thyroid cancer database (DATHYRCA) has been active in Denmark since January 1, 1996, no assessment of data quality has been performed. The purpose of the study was to evaluate completeness and data validity in the Danish national clinical thyroid cancer database: DATHYRCA.Study design and settingNational prospective cohort. Denmark; population 5.5 million. Completeness of case ascertainment was estimated by the independent case ascertainment method using three governmental registries as a reference. The reabstracted record method was used to appraise the validity. For validity assessment 100 cases were randomly selected from the DATHYRCA database; medical records were used as a reference.ResultThe database held 1934 cases of thyroid carcinoma and completeness of case ascertainment was estimated to 90.9%. Completeness of registration was around or above 90% in most instances. Perfect agreement on the diagnosis of thyroid carcinoma was found, both inter- and intra-observer, and κ values of selected variables showed overall good to excellent agreement.ConclusionIn a setup with public health insurance, personal identity numbers and extended governmental databases, it is possible to establish national clinical cancer databases with a satisfactory completeness and validity. The DATHYRCA database is considered reliable in terms of describing thyroid carcinoma at a national level.     

Geographic variation in diagnostic and treatment interval,cancer stage and mortality among colorectal patients – An international comparison between Denmark and Scotland using data-linked cohorts

BackgroundRurald wellers with colorectal cancer have poorer outcomes than their urban counterparts. The reasons why are not known but are likely to be complex and be determined by an interplay between geography and health service organization. By comparing the associations related to travel-time to primary and secondary healthcare facilities in two neighbouring countries, Denmark and Scotland, we aimed to shed light on potential mechanisms.MethodsAnalysis was based on two comprehensive cohorts of patients diagnosed with colorectal cancer in Denmark (2010−16) and Scotland (2007−14). Associations between travel-time and cancer pathway intervals, tumour stage at diagnosis and one-year mortality were analysed using generalised linear models. Travel-time was modelled using restricted cubic splines for each country and combined. Adjustments were made for key confounders.ResultsTravel-time to key healthcare facilities influenced the diagnostic experience and outcomes of CRC patients from Scotland and Denmark to some extent differently. The longest travel-times to a specialised hospital appeared to afford the most rapid secondary care interval, whereas moderate travel-times to hospital (about 20−60 min) appeared to impact on later stage and greater one-year mortality in Scotland, but not in Denmark. A U-shaped association was seen between travel-time to the GP and one year-mortality.ConclusionsThis is the first international data-linkage study to explore how different national geographies and health service structures may determine cancer outcomes. Future research should compare more countries and more cancer sites and evaluate the impact and implications of differences in national health service organisation.     

Survival of breast cancer patients in German-Danish border regions – A registry-based cohort study

Background and AimDenmark reports slightly lower breast cancer survival before 2010 than its neighbouring country Germany. Previous research is limited by lacking stage and treatment information. This study aims to investigate differences in breast cancer survival between the bordering regions Schleswig-Holstein (Germany), Southern Denmark and Zealand (Denmark) using registry data including stage and treatment information.MethodInvasive female breast cancer cases diagnosed during 2004−2013 with follow up through 31st December 2014 were extracted from cancer registries. Cases notified by death certificates only and those aged 90+ years were excluded. Kaplan-Meier curves and log-rank tests were computed. Cox regression analysis was conducted with adjustment for year of diagnosis, age, stage, and treatment.ResultsThe analytical sample included 42,966 cases. Kaplan-Meier curves and log-rank tests show significant survival differences between the regions. The Cox regression model adjusted for year of diagnosis and age shows significantly worse overall survival of breast cancer patients in both Danish regions compared to Schleswig-Holstein with hazard ratios (HR) of 1.09 (95 % CI: 1.04; 1.15) for patients from Southern Denmark (SD) and 1.25 (95 % CI: 1.18; 1.32) for residents of Zealand (ZL). This effect diminished after adjustment for stage and treatment (HR: 1.05 (SD), 1.09 (ZL) 95 % CI: 0.99; 1.10 (SD), 1.03; 1.15 (ZL)).ConclusionSurvival differences can be explained by differing stage distribution and treatment administration, which formerly were more favourable in Schleswig-Holstein. The survival gap will probably close due to Denmark’s national screening program and increased use of adjuvant cancer therapy.     

Predictors of non-participation in cervical screening in Denmark

PurposeThe aims of this study were to identify demographic and socio-economic predictors of non-participation in cervical screening in Denmark, and to evaluate the influence of health care use on screening participation.MethodsA population based register study was undertaken using data from the Central Population Register, the national Patobank, and Statistics Denmark. The study included women aged 25–54 years on 1st of January 2002, living in Denmark during the next 5 years, and without a history of total hysterectomy, N = 1,052,447. Independent variables included age, civil status, nationality, level of education, and use of health care. Associations with non-participation in screening were determined with logistic regression.ResultsMain predictors of non-participation were limited or no contact with dental services (odds ratio (OR) = 2.36), general practitioners (OR = 1.75), and high age (OR = 1.98). Other important factors for non-participation were primary school education only (OR = 1.53), not being married (OR = 1.49), and foreign nationality (OR = 1.32).ConclusionA 2–1.5-fold difference in non-participation in cervical screening in Denmark was found across various population sub-groups. Increased screening compliance among women with primary school education only, and limited or no use of primary health care services in general could potentially diminish the current social inequalities in cervical cancer incidence, and thus decrease the overall high incidence of this disease in Denmark.     

Body condition score,morphometric measurements and estimation of body weight in mature Icelandic horses in Denmark

Background

Obesity is related to the development of several diseases like insulin resistance and laminitis in horses. The prevalence of obesity among mature Icelandic horses in Denmark has not been investigated previously. This study aimed to find the prevalence of obesity, to compare body condition score (BCS) based on owner perception with that of an experienced person and to correlate the BCS to body weight (BW) and morphometric measures in a group of mature Icelandic horses in Denmark. A total of 254 Icelandic horses (≥4 years; 140 geldings, 105 mares, 9 stallions) from 46 different farms were included. All horses were assigned a BCS on a scale from 1 to 9 (1 is poor, 5 is moderate and 9 is extremely fat) by their owner and by an experienced person. Two weight tapes were used to assess BW. Girth circumference (GC), neck circumference (NC) and height at withers (HW) were measured, and the GC:HW and NC:HW ratios were calculated.

Results

Categorising the horses into four groups, 5.9 % were underweight (BCS 3–4), 70.1 % were optimal (BCS 5–6), 13.8 % were overweight (BCS 7) and 10.2 % were obese (BCS 8–9). The GC:HW and NC:HW ratios increased with increasing BCS, as did the BW estimated with the weight tapes. A GC:HW ratio >1.21 might indicate overweight or obesity in Icelandic horses. Horse owners underestimated the BCS of their horses compared to an experienced person.

Conclusions

The results from this study show that 24.0 % of mature Icelandic horses in Denmark are overweight or obese, and that owners tend to underestimate the BCS of their Icelandic horses. The GC:HW ratio might indicate overweight or obesity, however, the ratio for Icelandic horses is different than reported for horses and ponies of other breeds.

     

Denmark between liberalism and nationalism

Abstract

What explains the restrictive turn towards immigrants in European countries like Denmark? Are countries returning to nationalism, or are they following a general European trend towards a perfectionist, even ‘repressive’ liberalism that seeks to create ‘liberal people’ out of immigrants? Recent developments in Danish policies of integration and citizenship, education and anti-discrimination suggest a combination of these two diagnoses. The current Danish ‘integration philosophy’ leaves behind a previous concern with private choice and equal rights and opportunities to emphasize other historical elements, especially the duty to participate in upholding democracy and the egalitarian welfare community, and to promote autonomous and secular ways of life. However, the virtues of this ‘egalitarian republicanism’ are seen by right-of-centre intellectuals and politicians as rooted in a wider Christian national culture that immigrants must acquire in order to become full citizens.     

Spatial and temporal variations in the White-tailed Eagle Haliaeetus albicilla breeding diet revealed by prey remains

ABSTRACT

Capsule: Despite its population increase, the White-tailed Eagle Haliaeetus albicilla has not become food-limited, and does not pose a serious threat to birds of conservation concern in the region east of the Baltic Sea.

Aims: We aimed to test variations in the main prey groups and dietary niche breadth of White-tailed Eagles through the years and along an environmental gradient as well as to evaluate the extent of predation on bird species of conservation concern.

Methods: Prey remains were collected during nestling ringing from successful nests located in Lithuania.

Results: The frequency of the prey groups varied along an environmental gradient, with a general pattern of increasing avian prey consumed by pairs breeding in areas with less abundant aquatic habitats. The frequency of alternative prey (i.e. terrestrial birds, mammals) and dietary niche breadth did not increase between 2005 and 2018 and during which time the White-tailed Eagle population nearly doubled. Instead, the occurrence of Northern Pike Esox lucius remains, which was the most frequent single prey species, increased throughout the study period. Bird species of conservation concern constituted only a small fraction of all the prey identified.

Conclusions: The White-tailed Eagle has not become more dependent on alternative prey despite its population increase.     

New Horizons in Skeletal Physiology and Pathophysiology

ObjectiveTo review new discoveries that revisit our current thinking on the genesis of osteoporosis using hypogonadal and thyrotoxic bone loss as examples.MethodsWe focus on cell biologic, mouse genetic, and human studies that have established a direct action of the interior pituitary hormones follicle-stimulating hormone and thyrotropin on the skeleton and discuss emerging clinical evidence for a novel pituitary-bone axis in humans that bypasses master endocrine organs, namely the ovaries and thyroid gland.ResultsThe cataloguing of human mutations, the use of genetically modified mice that recapitulate human disease, and the rapid growth of genomic sciences have together had a profound impact on how basic research is translated into clinical practice. The skeleton has become a paradigm for the application of such advances to an extent that hitherto unrecognized physiologic and pathophysiologic findings have emerged. We propose that hypogonadal and thyrotoxic bone loss are not solely due to changes in the level of master hormones, but instead also arise from the direct action of anterior pituitary hormones on the skeleton.ConclusionsWe predict a pituitary-bone axis in which pituitary hormones bypass traditional endocrine targets to affect the skeleton directly with remarkable sensitivity. New therapeutic targets thus become a likely possibility. (Endocr Pract. 2010;16:874-881)     

Secular change in size at birth from 1973 to 2003: national data from Denmark

Objective: To explore whether birth weight (BW) has been increasing in Denmark at the same level as in other countries and whether this increase is paralleled by an increase in birth length (BL) or whether body proportionality, expressed as ponderal index (PI), has changed. Research Methods and Procedures: This study used data analysis of information from The Danish Medical Birth Registry including all single live births in Denmark from 1973 to 2003 (n = 1,863,456). BW, BL, gestational age, maternal age, and smoking status (only from 1991 on) were measured. Results: Mean BW increased steadily during the period (160 grams; equivalent to ～5 g/yr) at a rate higher than that reported from other countries. BL showed only a minor increase (2.4 mm), leading to an increase in PI (0.8 kg/m³) during the period. Controlling for the effect of increasing maternal age and decreasing gestational age and maternal smoking prevalence (only data after 1991), there was still an increase in BW of ～4 g/yr. Discussion: During the last 30 years, neonates have become bigger, with a larger relative increase in BW than BL, leading to an increase in PI. The increasing BW and PI, which may be caused by increased maternal weight, could further promote the obesity epidemic.     

政府补偿与监管机制改革对公立医疗卫生机构收支状况的影响分析

目的 分析政府补偿与监管机制改革前后闵行区公立医疗卫生机构的收支及结构变化,并与上海市同期平均水平进行比较,探索研究政府补偿与监管机制改革对公立医疗卫生机构收支状况的影响。方法 进行问卷调查和二手数据分析。结果 改革后,闵行区公立医疗卫生机构的医疗与药品收入比例趋于合理,医疗费用得到控制,但政府财政补助水平仍有待提高。结论 政府应确保公立医院财政投入水平,落实取消药品加成后的相应补偿。     

A secure SNP panel scheme using homomorphically encrypted K-mers without SNP calling on the user side

Background

Single Nucleotide Polymorphism (SNP) in the genome has become crucial information for clinical use. For example, the targeted cancer therapy is primarily based on the information which clinically important SNPs are detectable from the tumor. Many hospitals have developed their own panels that include clinically important SNPs. The genome information exchange between the patient and the hospital has become more popular. However, the genome sequence information is innate and irreversible and thus its leakage has serious consequences. Therefore, protecting one’s genome information is critical. On the other side, hospitals may need to protect their own panels. There is no known secure SNP panel scheme to protect both.

Results

In this paper, we propose a secure SNP panel scheme using homomorphically encrypted K-mers without requiring SNP calling on the user side and without revealing the panel information to the user. Use of the powerful homomorphic encryption technique is desirable, but there is no known algorithm to efficiently align two homomorphically encrypted sequences. Thus, we designed and implemented a novel secure SNP panel scheme utilizing the computationally feasible equality test on two homomorphically encrypted K-mers. To make the scheme work correctly, in addition to SNPs in the panel, sequence variations at the population level should be addressed. We designed a concept of Point Deviation Tolerance (PDT) level to address the false positives and false negatives. Using the TCGA BRCA dataset, we demonstrated that our scheme works at the level of over a hundred thousand somatic mutations. In addition, we provide a computational guideline for the panel design, including the size of K-mer and the number of SNPs.

Conclusions

The proposed method is the first of its kind to protect both the user’s sequence and the hospital’s panel information using the powerful homomorphic encryption scheme. We demonstrated that the scheme works with a simulated dataset and the TCGA BRCA dataset. In this study, we have shown only the feasibility of the proposed scheme and much more efforts should be done to make the scheme usable for clinical use.

     

Prevalence of tick-borne encephalitis virus antibodies in dogs from Denmark

Background  

Large regions of central and eastern Europe are recognized as areas where tick-borne encephalitis virus (TBEV) is endemic, including countries neighbouring Denmark. It is therefore timely and relevant to determine if TBEV infections occur in Denmark. This study investigates the presence of antibodies against TBEV in a cross-section of the Danish canine population to assess the level of exposure to TBEV and possibly identify TBEV microfoci in Denmark.     

Quantifying patch‐specific seed dispersal and local population dynamics to estimate population spread of an endangered plant species

AimHabitat loss and fragmentation impose high extinction risk upon endangered plant species globally. For many endangered plant species, as the remnant habitats become smaller and more fragmented, it is vital to estimate the population spread rate of small patches in order to effectively manage and preserve them for potential future range expansion. However, population spread rate has rarely been quantified at the patch level to inform conservation strategies and management decisions. To close this gap, we quantify the patch‐specific seed dispersal and local population dynamics of Minuartia smejkalii, which is a critically endangered plant species endemic in the Czech Republic and is of urgent conservation concern.LocationŽelivka and Hrnčíře, Czechia.MethodsWe conducted demographic analyses using population projection matrices with long‐term demographic data and used an analytic mechanistic dispersal model to simulate seed dispersal. We then used information on local population dynamics and seed dispersal to estimate the population spread rate and compared the relative contributions of seed dispersal and population growth rate to the population spread rate.ResultsWe found that although both seed dispersal and population growth rate in M. smejkalii were critically limited, the population spread rate depended more strongly on the maximal dispersal distance than on the population growth rate.Main conclusionsWe recommend conservationists to largely increase the dispersal distance of M. smejkalii. Generally, efforts made to increase seed dispersal ability could largely raise efficiency and effectiveness of conservation actions for critically endangered plant species.     

Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans,Baboons, and Pigs from Different Geographical Regions

BackgroundThe whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found in primates.

Methods and Findings

We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes of Trichuris recovered from a human and a porcine host in China and from a françois’ leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively) suggesting that they represented different species. Trichuris from the olive baboon in US was genetically related to human Trichuris in China, while the other from the hamadryas baboon in Denmark was nearly identical to human Trichuris from Uganda. Baboon-derived Trichuris was genetically distinct from Trichuris from françois’ leaf monkey, suggesting multiple whipworm species circulating among non-human primates. The genetic and protein distances between pig Trichuris from Denmark and other regions were roughly 9% and 6%, respectively, while Chinese and Ugandan whipworms were more closely related.

Conclusion and Significance

Our results indicate that Trichuris species infecting humans and pigs are phylogenetically distinct across geographical regions, which might have important implications for the implementation of suitable and effective control strategies in different regions. Moreover, we provide support for the hypothesis that Trichuris infecting primates represents a complex of cryptic species with some species being able to infect both humans and non-human primates.     

Baseline Levels and Temporal Stability of 27 Multiplexed Serum Cytokine Concentrations in Healthy Subjects

BackgroundCytokines are humoral molecules that elicit regulatory function in immunologic pathways. The level and type of cytokine production has become critical in distinguishing physiologic from pathologic immune conditions. Cytokine profiling has become an important biomarker discovery tool in monitoring of the immune system. However, the variations in cytokine levels in individual subjects over time in healthy individuals have not been extensively studied. In this study, we use multiplex bead arrays to evaluate 27 analytes in paired serum samples taken seven days apart from 144 healthy individuals in order to assess variations over a short time period.MethodsFluorescent bead-based immunoassay (Luminex) was used to measure 27 analytes in serum samples. Measurements were performed on matched samples from 144 healthy donors. To assess inter-plate variability, one arbitrarily selected serum sample was analyzed on each of the first ten plates as bridge sample. ResultsUsing the bridge sample, we showed minimal inter-plate variations in the measurement of most analytes. In measurement of cytokines from the 144 patients at two time points, we found that three cytokines (IL-2, IL-15 and GM-CSF) were undetectable and five analytes (RANTES, MCP-1, VEGF, MIP-1β and PDGF-BB) showed significant difference in concentrations at Day 0 compared to Day 7. ConclusionsThe current study demonstrated higher variations in cytokine levels among individuals than were observed for samples obtained one week apart from identical donors. These data suggest that a serum sample from each subject for use as a baseline measurement is a better control for clinical trials rather than sera from a paired cohort.     

超声靶向微泡破坏与载药/载基因纳米粒联合应用的生物物理学机制及应用研究进展

超声靶向微泡破坏(ultrasound-targeted microbubble destruction, UTMD)能够安全、高效、简便地递送药物与基因,是当前超声医学领域的研究热点,其机制主要涉及超声辐照微泡引起的空化效应及其二级效应、内吞作用与声辐射力。近年来,随着生物医学材料科学迅猛发展,纳米载药系统取材更加广泛,制备方法愈发精良,载药量日益提高。将纳米载药系统与UTMD进行联合,可以扬长避短,为肿瘤等多种疾病的治疗带来新的思路与希望。本文旨在对UTMD与载药/载基因纳米粒联合应用的生物物理学机制及应用研究进行综述并提出展望。     

CHANGES IN CLICK SOURCE LEVELS WITH DISTANCE TO TARGETS: STUDIES OF FREE-RANGING WHITE-BEAKED DOLPHINS LAGENORHYNCHUS ALBIROSTRIS AND CAPTIVE HARBOUR PORPOISES PHOCOENA PHOCOENA

ABSTRACT

Probably all odontocetes use echolocation for spatial orientation and detection of prey. We used a four hydrophone “Y” array to record the high frequency clicks from free-ranging White-beaked Dolphins Lagenorhynchus albirostris and captive Harbour Porpoises Phocoena phocoena. From the recordings we calculated distances to the animals and source levels of the clicks. The recordings from White-beaked Dolphins were made in Iceland and those from Harbour Porpoises at Fjord & Baelt, Kerteminde, Denmark during prey capture. We used stringent criteria to determine which clicks could be defined as being on the acoustic axis. Two dolphin and nine porpoise click series could be used to track individual animals, which presumably focused on the array hydrophones or a fish right in front of the array. The apparent source levels of clicks in the individual tracks increased with range. One individual White-beaked Dolphin and three Harbour Porpoises regulate their output signal level to nearly compensate for one-way transmission loss while approaching a target. The other dolphin regulated the output differently. For most of the recordings the sound level at the target remains nearly constant and the echo level at the animal increases as it closes on the target.     

Tavola Rotonda Sulla Ontogenesi,Conservazione e Germinazione Del Seme Roma 22–23 Maggio 1978

Abstract

Diversities and interfaces in the zonal analysis of vegetation. – The attention is called to the growing complexity of ecological and phytogeo-graphical problems emerging from the examination of the diversities of the vegetal landscape. The trend towards typologies, zonations both in the altitudinal sense and latitudinal sense has produced very useful schemes and frameworks which are fundamental references. But problems become more and more extensive and critical in the areas of transition between these types and these zones. These areas, which are particularly fragile, being as they are the centre of delicate balancing processes, are expanding – mostly for anthropical action – to such extent as to become wider than the typical zones codified by usual schemes. Therefore it is required a more intense research even for exigencies of conservation of the land, vegetation and values of human interest.