Family history and prognosis of prostate cancer

Background: Prostate Cancer (PCa) is the second most common malignancy among men in the world. In Sweden about 10,000 new cases are diagnosed each year. Mortality rates have been rather stable but have declined the past decades due to early diagnosis and treatment at the expense of overtreatment. High age, ethnic origin and family history are known risk factors. The strongest predictor for poor prognosis is tumour differentiation at diagnosis. Previous studies have suggested that men with family history of mortal PCa, themselves are at higher risk for mortal disease. In twin studies it has been demonstrated that the contribution of shared genome to PCa risk is substantial. Aims: The overall aim is to explore the importance of family history as a prognostic marker for prognosis in PCa. Specifically, in Paper I: To estimate the concordance of tumour differentiation among pairs of brothers with PCa. Paper II: To estimate the relative differences in risk of non-low PCa between different types of brothers. Paper III: To estimate if men with family history of PCa have higher risk of postoperative histopathological upgrading or upstaging comparted to men without family history. Paper IV: To evaluate the prognostic value of the HOXB13 G84E mutation in a screening cohort. Methods: PCBaSe provides a population-based database with the National Prostate Register (NPCR) linked to several other National registers in Sweden. In Paper I 1,022 pairs of brothers with PCa diagnosed 1996-2006 were identified. The relative risk for the second brother to be concordant in tumour differentiation (Gleason score) was estimated with SIR. In Paper II 4,262 pairs of brothers with PCa diagnosed 1996-2012 were identified. Using the Swedish twin register and the Multi-Generation Register, all pairs of brothers were stratified by type of fraternity. Tumour characteristics were compared and the risk of concordance for non-low risk PCa was estimated. In Paper III, 6,638 men with low risk PCa treated with prostatectomy 2003- 2012 were identified. Of those, 1,696 (26%) had family history of PCa among FDRs. The excess risk of postoperative upgrading or upstaging was estimated using logistic regression comparing men with and without family history of PCa. In Paper IV the study population was based on a screening cohort in Stockholm County 2012-2015. 27,578 men with Prostate Specific Antigen (PSA) >1 were offered genetic testing with 232 Single Nucleotide Polymorphisms (SNPs) associated with PCa. Men with PSA>3 were offered biopsies. Carriers of HOXB13 G84E were compared to non-carriers for risk of significant PCa. Results: In Paper I, we found an overall risk of concordance in tumour differentiation of SIR 3.1 (95% CI, 2.9–3.3). SIR for brothers of men with high grade Gleason score was 4.00 (95% CI, 2.63–5.82). In Paper II, the adjusted OR for concordance in non-low risk PCa among monozygotic twins was 3.85 (95% CI, 0.99-16.72) and for full brothers adjusted OR was 1.21 (95% CI, 1.04-1.39). In analyses restricted to pairs of brothers diagnosed within 4 years, the results were similar. In Paper III, the risk of postoperative upstaging among men with first- degree relatives (FDR's) with high grade or lethal PCa was OR 1.06 (95% CI, 0.76-1.47). For risk of upgrading, OR was 1.17 (95% CI, 0.91-1.50). In Paper IV, the prevalence of HOXB13 G84E was 1.3% of 27,578 men with PSA between 1 and 100. The overall risk of any cancer for HOXB13 G84E carriers was OR 4.67 (95% CI, 2.93-7.73). The risk for clinically significant cancer was OR 2.10 (95% CI, 1.34-3.26). Conclusions: Men with brothers with high grade PCa are at higher risk themselves for high grade PCa, which have an impact on counselling these men. Shared genetic factors seem to increase the risk of non-low risk PCa. The highest increase in risk is observed among monozygotic twins, although with non-significant estimate. Men with familial history of high risk or lethal PCa are not at higher risk of postoperative upstaging or upgrading after prostatectomy for low risk PCa, compared to men without family history. Those men can comfortable be recommended active surveillance on the same basis as men without family history. Carriers of the rare HOXB13 G84E mutation are increased risk for clinically significant and HOXB13 G84E and we argue that HOXB13 G84E should be included for men recommended genetic counselling

INTENT-BASED SERVICE AUTOMATION FOR 5G CORE NETWORK FUNCTION SLICING

The techniques presented herein maintain network function (NF) resource adjacencies regardless of the shared or dedicated nature of the NF and independent of the segmentation of the NF\u27s cluster resources across geographic management domains. To achieve this, the techniques use intent-based networking models in order to create NF resources that facilitate the network slice creation and resource allocation. More specifically, the techniques utilize a Yet Another Next Generation (YANG) model representation of a network slice to facilitate creation and state management of all NFs associated with a network slice instance. The YANG model enables inter-site and intercluster adjacencies where cloud-native container network interface (CNI) communications is invalid. This also provides reference points for inter-domain orchestration between the mobility NFs, the underlying data center switching resources, and wide area network (WAN) transport slices

Comparing profitability of organic vs. conventional arable farming in Scania

Efterfrågan på ekologiska råvaror och produkter ökar årligen och det inhemska behovet överstiger utbudet. Arbetet visar på en fortsatt ökning av efterfrågan på ekologiska livsmedel i Sverige. Syftet med vårt examensarbete var att undersöka den ekonomiska skillnaden mellan två typer av odlingssystem i ekologisk odling, dels traditionell ekologisk etablering men också no-till etablering. No-till fungerar precis som direktsådd, men vid etablering i ett ekologiskt system sår man in en mellan- eller fånggröda mellan såraderna, vilka sedan fungerar som ogräsbekämpning. Dessa två etableringsmetoder skall sedan jämföras med dagens konventionella odlingssystem (strip-tillage). Det innebär kortfattat att marken endast bearbetas i den rad där utsädet ska placeras. Ytan mellan såraderna lämnas därmed orörd. Detta var en fallstudie som genomfördes på uppdrag av AB Gårdstånga Nygård, en växtodlingsgård i Flyingebygden, strax norr om Lund. Kalkylering har genomförts med största fokus på de två ekologiska etableringsmetoderna med växtföljden Vårkorn – Åkerböna – Höstvete – Raps – Höstvete. Sedan har de två växtföljdernas ekonomiska netto jämförts med gårdens nuvarande konventionella växtföljd netto. De två ekologiska etableringsmetoderna skiljer sig en del från varandra. Den för Sverige traditionella etableringen med flera jordbearbetningar för att utarma ogräset visade sig ha en högre etableringskostnad/hektar samt ett något lägre netto på samtliga grödor. No-till (direktsådd) som är tänkt att användas på AB Gårdstånga Nygård visade på ett högre netto, mycket tack vare en lägre etableringskostnad än det traditionella systemet. Med ett no-till system körs det mindre timmar i fält vilket dels ger en lägre bränsleåtgång, dels är mer miljövänligt. Det gör också att odlingen blir mindre känslig för ett högre bränslepris. Den goda prisbilden för ekologisk produktion möjliggörs genom att avsalupriset inte är direkt bundet till den internationella marknaden utan tillgång och efterfrågan inom Sverige styr prisbilden. Även miljöstöden bidrar till en större intäkt för ekologiskt producerade varor, exempelvis ger rapsen 2200 kronor/hektaret och år. I litteraturstudien beskrivs no-till systemet med dess för- och nackdelar, som är ett obeprövat system i Sverige. Det har inte tagits med någon känslighetsanalys gällande extra kostnader för att använda detta system som etableringsmetod. I litteraturstudien framgår att systemet ska kunna fungera väl i södra Sverige och författarna har därför utgått från det i kalkyleringen. Skördenivåer som används i kalkylerna är beräknat till 70 procent av en konventionell skörd i området vilket styrks genom efterforskning i litteraturstudien. Enligt Ulrik Lovang kan skördenivåerna uppgå till 90 procent av konventionell nivå vid en väl etablerad gröda vilket uppnåtts på gårdar i Östergötland. Målet med fallstudien är uppnått, kalkylerna visar på ett positivt netto vid omläggning av produktionen från konventionell till ekologisk odling. Både no-tillsystemet och det mer traditionella visar på att alla ekologiska grödor hade ett bättre ekonomiskt netto än AB Gårdstånga Nygårds konventionella system. Den enda grödan som inte kunnat jämföras är sockerbetor vilket i dagsläget inte kommer odlas ekologiskt.Demand for organic raw material and products are increasing annually, while domestic demand is increasing above supply (Ryegård CR, 2014). The research the report shows a continuing rise for organic food in Sweden. The aim of this thesis was to investigate the economic difference between the two types of cropping systems in organic farming, in comparison to today's conventional cropping systems (strip-tillage). This was a case study that was conducted on behalf of AB Gårdstånga Nygård, an arable farm in the Flying district, just north of Lund. Calculation Rings have been conducted with the greatest focus on two ecological establishment methods of crop rotation Spring barley - Field beans - Winter wheat - Rape - Winter wheat. After that the two rotations ' financial net are compared with the farm's current conventional crop rotation net. The two organic establishment methods differ somewhat from each other. The traditional establishment in Sweden with several soil processing to deplete the weed showed a higher establishment cost / hectare, and a slight decrease in net for all crops. No-till (direct sowing) that is meant to be used on AB Gårdstånga Nygård showed a higher net, thanks largely to a lower establishment cost than the traditional system. With a no-till system there will be less driving in the field and that resulting in lower fuel consumption. This system is both more environmentally friendly and to be less sensitive to higher fuel price. The favorable pricing of organic production in Sweden is made possible by a price not directly tied to the international market, but in Sweden the price is controlled by supply and demand. Also environmental support contributes to greater revenue for organically produced products, for example rape gives 2200 SEK / hectare and year. In our literature study the no-till system and its pros and cons are described, since it is an untested system in Sweden .We have not made any sensitivity analysis regarding additional costs for using this system as a production method. In the literature, it appears that the system can function well in southern Sweden and we have therefore assumed this in the calculation. Crop yields are estimated to be 70 percent of a conventional harvest in the area as evidenced by reading literature. According to the Swedish advisor, Ulrik Lovang who is famous for his work whit organic farming, harvest levels can reach 90 percent by conventional level for a well- established crop which farmers in Östergötland achieved. The calculations in this study show a net positive to shift production from conventional farming to organic. The new system they will try, and the more traditional shows that all organic crops had a better economic net than AB Gårdstånga Nygårds conventional systems. The only crop we have not been able to compare is sugar-beets which will not be grown organically in the current situation at AB Gårdstång Nygård farm

Active bacterial community structure along vertical redox gradients in Baltic Sea sediment

Community structures of active bacterial populations were investigated along a vertical redox profile in coastal Baltic Sea sediments by terminal-restriction fragment length polymorphism (T-RFLP) and clone library analysis. According to correspondence analysis of T-RFLP results and sequencing of cloned 16S rRNA genes, the microbial community structures at three redox depths (179 mV, -64 mV and -337 mV) differed significantly. The bacterial communities in the community DNA differed from those in bromodeoxyuridine (BrdU)-labeled DNA, indicating that the growing members of the community that incorporated BrdU were not necessarily the most dominant members. The structures of the actively growing bacterial communities were most strongly correlated to organic carbon followed by total nitrogen and redox potentials. Bacterial identification by sequencing of 16S rRNA genes from clones of BrdU-labeled DNA and DNA from reverse transcription PCR (rt-PCR) showed that bacterial taxa involved in nitrogen and sulfur cycling were metabolically active along the redox profiles. Several sequences had low similarities to previously detected sequences indicating that novel lineages of bacteria are present in Baltic Sea sediments. Also, a high number of different 16S rRNA gene sequences representing different phyla were detected at all sampling depths

Health-related quality of life, utility, and productivity outcomes instruments: ease of completion by subjects with COPD

An important outcome of any clinical intervention is the change in the subject's own perceived state of health. This can be categorized as health-related quality of life (HRQL), utility (preference-based health state), and daily life performance. 174 Swedish subjects with chronic obstructive pulmonary disease (COPD) (mean age 64.3 ± 12 years) completed five self-administered questionnaires: Short Form 36 (SF-36), St George's Respiratory Questionnaire (SGRQ), EuroQol-5D (EQ-5D), Health States-COPD (HS-COPD), and Work Productivity and Activity Impairment Questionnaire for COPD (WPAI-COPD). The subjects scored these outcomes instruments for ease of completion using a 5-point scale. The time taken to complete them was noted and the administrators' opinion of the subjects' comprehension of the questionnaires recorded using a 4-point scale. A score of 1–3 ("very easy" to "acceptable") was recorded by 92% of subjects for the SF-36, 90% for SGRQ, 80% for EQ-5D, 83% for WPAI-COPD, and 53% for HS-COPD. The HS-COPD was graded "very difficult" to complete by 21% of subjects compared with 3–5% of subjects for the other questionnaires. The mean time taken to complete all questionnaires was 39 minutes, and the large majority of subjects scored "good" for understanding by the administrator. Age correlated significantly with the degree of the subject's opinion of the ease of completion of five outcomes instruments, while the influence of gender, socio-economic status and disease severity was not statistically significant

Analysis of a spatial gene expression database for sea anemone Nematostella vectensis during early development

International audienceThe spatial distribution of many genes has been visualized during the embryonic development in the starlet sea anemone Nematostella vectensis in the last decade. In situ hybridization images are available in the Kahi Kai gene expression database, and a method has been developed to quantify spatial gene expression patterns of N. vectensis. In this paper, gene expression quantification is performed on a wide range of gene expression patterns from this database and descriptions of observed expression domains are stored in a separate database for further analysis

Thoracolumbar vertebral fractures in Sweden: an analysis of 13,496 patients admitted to hospital

National Longitudinal data of thoracolumbar fracture incidence, trends or mortality rates are lacking. The correlation between admissions and operations of thoracolumbar vertebral fractures has not been investigated. The aim of our nationwide population-based epidemiological study was to analyse the incidence, admissions, operations, and case fatality rate among patients with thoracolumbar vertebral fractures admitted to hospital in Sweden. The Swedish Hospital Discharge Register (SHDR) and the Cause of Death Register (CDR) were linked to determine the incidence of surgical interventions, trends, characteristics of the patients, and case fatality rate for thoracolumbar vertebral fractures based on comprehensive national data. The annual incidence of thoracolumbar fractures was on average 30 per 100,000 inhabitants and did not change considerably during the study period. Among patients younger than 60 years of age the annual incidence was 13 per 100,000 and was twice as high in men compared to women. The proportion operated on was 15%. In the age-group 60 years and older the majority were women. In this group two percent were operated on. However, males were operated on twice as often as women. The 90-day case-fatality rate after surgery was 1.4%. This information may assist health care providers in health care planning. Moreover, these data can also be used for power calculations when planning future clinical studies

Virus Diversity and Loads in Crickets Reared for Feed: Implications for Husbandry

Insects generally have high reproductive rates leading to rapid population growth and high local densities; ideal conditions for disease epidemics. The parasites and diseases that naturally regulate wild insect populations can also impact when these insects are produced commercially, on farms. While insects produced for human or animal consumption are often reared under high density conditions, very little is known about the microbes associated with these insects, particularly those with pathogenic potential. In this study we used both target-free and targeted screening approaches to explore the virome of two cricket species commonly reared for feed and food, Acheta domesticus and Gryllus bimaculatus. The target-free screening of DNA and RNA from a single A. domesticus frass sample revealed that only 1% of the nucleic acid reads belonged to viruses, including known cricket, insect, bacterial and plant pathogens, as well as a diverse selection of novel viruses. The targeted screening revealed relatively high levels of Acheta domesticus densovirus, invertebrate iridovirus 6 and a novel iflavirus, as well as low levels of Acheta domesticus volvovirus, in insect and frass samples from several retailers. Our findings highlight the value of multiple screening approaches for a comprehensive and robust cricket disease monitoring and management strategy. This will become particularly relevant as-and-when cricket rearing facilities scale up and transform from producing insects for animal feed to producing insects for human consumption

Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney.

Acute tubular necrosis (ATN), elicited by ischemia and/or toxicity, is a potentially life-threatening condition. Histologically, ATN corresponds to necrosis and detachment of renal tubular epithelial cells. However, the tubules possess a considerable regenerative capacity and may be restored. We have previously identified a scattered population of progenitor-like cells within the proximal tubules, sharing marker expression with the parietal epithelial cells of Bowman's capsule as well as with renal tubules regenerating after ATN. In the present analysis, we use transmission electron microscopy, immunoelectron microscopy and immunofluorescence of human kidney cortex to further explore these cells. We demonstrate that the cells are smaller and have drastically fewer mitochondria than the surrounding proximal tubule cells. They also display strong expression of several structural proteins such as vimentin, collagen-7A1 and the tight junction protein claudin-1. To functionally assess these cells, we also developed a novel human kidney explant model of ATN demonstrating that the cells are more resilient to injury than the surrounding proximal tubular cells. Taken together the results suggest a novel robust cell type with a contrasting biological role to that of the bulk of proximal tubular epithelium