To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Multi-analyte assays with algorithmic analyses (MAAAs) use combinations of circulating and clinical markers including omics-based sources for diagnostic and/or prognostic purposes. Assessing MAAAs is challenging under existing health technology assessment (HTA) methods or practices. We undertook a scoping review to explore the HTA methods used for MAAAs to identify the criteria used for clinical research and reimbursement purposes.
This review included only non-companion (stand-alone) tests that are actionable and that have been evaluated by leading HTA or insurer/reimbursement bodies up to September 2017.
Twenty-five reports and articles evaluating seventeen MAAAs were examined, most of which have been developed in oncology. The two main models used were the EUnetHTA Core model and the Evaluation of Genomic Applications in Practice and Prevention ACCE framework. Clinical validity and utility criteria were used, as were economic, ethical, legal, and social aspects. Economic evidence on MAAAs was scarce, and there is no consensus on whether the perspectives used are sufficiently broad to include all relevant stakeholders.
Clinical utility and efficiency were the most used criteria, with stronger evidence needed linking the use of the algorithm with the clinical outcomes in real-life practice. HTA bodies must as well consider questions related to the analytical validity of MAAAs or with organizational aspects. The two main models, the EUnetHTA Core model and the ACCE framework, could be adapted to the assessment of MAAAs.
Lameness is a well-recognised welfare problem which causes suffering to the dairy cow and economic losses to the dairy industry. Major lesion incidence occurs in the claw (Logue et al., 1995). Claw lesions include those of the white line, solear haemorrhage and solear ulceration and are associated with damage to the underlying soft tissues and reductions in claw horn quality. Claw horn is formed from proliferation of epidermal cells in the stratum germinativum bordering the basement membrane and dermis (corium). Dermal-epidermal interactions are important in good quality horn formation and one aim of the study was to characterise physical dimensions of soft tissue containing these regions in female dairy cattle of varying ages. A second aim was to determine external claw dimensions and relate these to developmental processes within the animals.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
This chapter reviews the current knowledge of the molecular mechanisms controlling embryonic lung development in animal models from the initial specification of a small number of respiratory progenitor cells in the ventral foregut endoderm through the formation of the mature adult lung with regionally specialized epithelial, interstitial, and vascular compartments. In the second half of this chapter we introduce induced pluripotent stem cells (iPSCs) as a compelling new platform to study human lung biology at developmental time-points previously inaccessible to researchers. iPSCs offer the potential to generate functional lung tissue in vitro by translating the knowledge gained from studying respiratory system development in different animal models where many of the signaling pathways or airway branching mechanisms are evolutionarily conserved. There are many exciting possible applications of iPSC-derived lung tissue, including the ability to model human lung disease, screen novel drug therapies, and ultimately generate functional, transplantable lung cells or 3-D tissues for those suffering from one of the many forms of end-stage lung disease.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
During one week in July 2012, two patients from the same ward at the municipal hospital in Vaasa, Finland, were diagnosed with septicaemia caused by Listeria monocytogenes. An outbreak investigation revealed eight concomitant cases of febrile gastroenteritis caused by L. monocytogenes on the same ward. Median age of the cases was 82 years and median incubation time for listerial gastroenteritis was 21 h (range 9–107). An additional 10 cases of invasive listeriosis caused by the same outbreak strain were identified across the whole country during the summer of 2012. Environmental investigation at the affected municipal hospital ward revealed ready-sliced meat jelly as the suspected source of the infection. During inspection of the meat jelly production plant, one pooled sample taken from a floor drain and a trolley wheel in the food processing environment was positive for the outbreak strain of L. monocytogenes. After the producer stopped the production of meat jelly, no further cases of listeriosis with the outbreak strain were identified via nationwide surveillance.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
In 2010, a marked increase in listeriosis incidence was observed in Finland. Listeria monocytogenes PFGE profile 96 was responsible for one-fifth of the reported cases and a cluster of PFGE profile 62 was also detected. Investigations revealed two fishery production plants with persistent Listeria contamination. It appears likely that the plants were at least partly responsible for the increase of listeriosis. Epidemiological investigation revealed that 57% (31/54) of cases with underlying immunosuppressive condition or medication reported eating gravad or cold-smoked fish. Two public notices were issued by THL and Evira informing which groups were most at risk from the effects of listeriosis and should therefore be cautious in consuming certain products. Systematic sampling of foods and adequate epidemiological investigation methods are required to identify the sources of Listeria infections. Continuous control measures at fishery production plants producing risk products are essential.
The Millimetre Astronomy Legacy Team 90 GHz (MALT90) survey aims to characterise the physical and chemical evolution of high-mass star-forming clumps. Exploiting the unique broad frequency range and on-the-fly mapping capabilities of the Australia Telescope National Facility Mopra 22 m single-dish telescope1, MALT90 has obtained 3′ × 3′ maps towards ~2 000 dense molecular clumps identified in the ATLASGAL 870 μm Galactic plane survey. The clumps were selected to host the early stages of high-mass star formation and to span the complete range in their evolutionary states (from prestellar, to protostellar, and on to
regions and photodissociation regions). Because MALT90 mapped 16 lines simultaneously with excellent spatial (38 arcsec) and spectral (0.11 km s−1) resolution, the data reveal a wealth of information about the clumps’ morphologies, chemistry, and kinematics. In this paper we outline the survey strategy, observing mode, data reduction procedure, and highlight some early science results. All MALT90 raw and processed data products are available to the community. With its unprecedented large sample of clumps, MALT90 is the largest survey of its type ever conducted and an excellent resource for identifying interesting candidates for high-resolution studies with ALMA.
In August 2012, an outbreak of gastroenteritis occurred among 88 persons attending a wedding reception at a resort/activity centre in Ylöjärvi, Finland. Of 39 interviewed guests, 23 met the case definition. Two persons were hospitalized. Epidemiological, laboratory and environmental investigations were conducted to characterize the outbreak and to recommend control measures. Investigation confirmed the presence of a new strain of norovirus GII.4 Sydney variant in stool specimens obtained from two wedding guests and on several environmental surfaces in the centre. In the questionnaire study, none of the foods or beverages served during the reception were significantly associated with the illness. Additional cases of gastroenteritis that occurred at the centre before and after the wedding reception supported the hypothesis of environmental transmission of norovirus. After thorough cleansing and disinfection and 1 week's quarantine, no new cases with symptoms typical for norovirus infection were identified at the centre.
In recent years, concerns have been highlighted in several jurisdictions, including Ireland, regarding abuse of over-the-counter codeine-containing medicines. On the 1st of August 2010, national regulatory guidelines aimed at limiting the supply of these medicines in Ireland came into force.
To study the effects of the new regulations on the use of non-prescribed codeine-containing medicines by psychiatric patients admitted to an Irish university teaching hospital before (n = 117) the regulations came into effect and 6 months afterwards (n = 126).
Participants completed a brief self-administered survey questionnaire about their use of over-the-counter codeine-containing medicines in the preceding 3 months.
Compared with before the introduction of the new regulations, there was a large decline in the reported ‘often’ or ‘regular’ use of codeine-containing medicines in the 3 months before admission (33.3% v. 17.4%, χ2 = 6.354, p = 0.01) and there was a reduction in the proportion of patients for whom others had expressed concerns about their frequency of use of such medications (15.5% v. 4.8%, χ2 = 7.29, p = 0.03). There was also a decline in the proportion of patients who stated that they would use codeine-containing medicines for either a ‘feel-good’ effect or to curb cravings (15.9% v. 1.9%, p < 0.01, two-tailed Fisher's exact test).
We conclude that tight regulations on the supply of non-prescription codeine-containing medicines have the potential to reduce the use and abuse of such medicines in patient populations availing of admission to psychiatry hospitals.
In 2010, 7/44 (16%) reported foodborne outbreaks in Finland were linked with raw beetroot consumption. We reviewed data from the national outbreak registry in order to hypothesize the aetiology of illness and to prevent further outbreaks. In the seven outbreaks, 124 cases among 623 respondents were identified. Consumption of raw beetroot was strongly associated with gastrointestinal illness (relative risk 8·99, 95% confidence interval 6·06–13·35). The illness was characterized by sudden onset of gastrointestinal symptoms; the median incubation time was 40 min and duration of illness 5 h. No common foodborne pathogens or toxins were found in either clinical or beetroot samples, but all tested beetroot samples were of poor quality according to total bacterial counts. Beta-haemolytic Pseudomonas fluorescens was detected in several beetroot samples but its effect on human health is unknown. No outbreaks were reported after the Finnish Food Safety Authority Evira advised against serving raw beetroot in institutional canteens.
The release fractions of the five elements in the ε-phase (99Tc,
97Mo, Ru, Rh, and Pd) as well as that of 238U are
reported for the reaction of two oxide fuels (ATM-103 and ATM-106) in
unsaturated tests under oxidizing conditions. The 99Tc release
fractions provide a lower limit for the magnitude of the spent fuel
reaction. The 99Tc release fractions indicate that a surface
reaction might be the rate controlling mechanism for fuel reaction under
unsaturated conditions and the oxidant is possibly
H2O2, a product of alpha radiolysis of water.
Molecular beam epitaxy has been used to grow GaInAsSb/AlGaAsSb double heterostructures, lattice matched to GaSb substrates, for diode laser emission at 2.3 μm. Doublecrystal x-ray diffraction measurements were used to determine alloy lattice constants, and photoluminescence and infrared absorption spectroscopies were used to determine the bandgaps of the GaInAsSb layers. Alloy compositions measured by Auger electron spectroscopy were consistent with measured lattice constants and bandgaps. Diode lasers fabricated from the double heterostructures were operated in the pulsed mode at room temperature with threshold current densities as low as 1.5 kA cm−2, differential quantum efficiencies as high as 50 percent, and output power as high as 900 mW per facet.