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Increasing evidence indicates that gut microbiota may influence colorectal cancer risk. Diet, particularly fibre intake, may modify gut microbiota composition, which may affect cancer risk. We investigated the relationship between dietary fibre intake and gut microbiota in adults. Using 16S rRNA gene sequencing, we assessed gut microbiota in faecal samples from 151 adults in two independent study populations: National Cancer Institute (NCI), n 75, and New York University (NYU), n 76. We calculated energy-adjusted fibre intake based on FFQ. For each study population with adjustment for age, sex, race, BMI and smoking, we evaluated the relationship between fibre intake and gut microbiota community composition and taxon abundance. Total fibre intake was significantly associated with overall microbial community composition in NYU (P=0·008) but not in NCI (P=0·81). In a meta-analysis of both study populations, higher fibre intake tended to be associated with genera of class Clostridia, including higher abundance of SMB53 (fold change (FC)=1·04, P=0·04), Lachnospira (FC=1·03, P=0·05) and Faecalibacterium (FC=1·03, P=0·06), and lower abundance of Actinomyces (FC=0·95, P=0·002), Odoribacter (FC=0·95, P=0·03) and Oscillospira (FC=0·96, P=0·06). A species-level meta-analysis showed that higher fibre intake was marginally associated with greater abundance of Faecalibacterium prausnitzii (FC=1·03, P=0·07) and lower abundance of Eubacterium dolichum (FC=0·96, P=0·04) and Bacteroides uniformis (FC=0·97, P=0·05). Thus, dietary fibre intake may impact gut microbiota composition, particularly class Clostridia, and may favour putatively beneficial bacteria such as F. prausnitzii. These findings warrant further understanding of diet–microbiota relationships for future development of colorectal cancer prevention strategies.
Bipolar disorder and schizophrenia are associated with increased mortality relative to the general population. There is an international emphasis on decreasing this excess mortality.
To determine whether the mortality gap between individuals with bipolar disorder and schizophrenia and the general population has decreased.
A nationally representative cohort study using primary care electronic health records from 2000 to 2014, comparing all patients diagnosed with bipolar disorder or schizophrenia and the general population. The primary outcome was all-cause mortality.
Individuals with bipolar disorder and schizophrenia had elevated mortality (adjusted hazard ratio (HR) = 1.79, 95% CI 1.67–1.88 and 2.08, 95% CI 1.98–2.19 respectively). Adjusted HRs for bipolar disorder increased by 0.14/year (95% CI 0.10–0.19) from 2006 to 2014. The adjusted HRs for schizophrenia increased gradually from 2004 to 2010 (0.11/year, 95% CI 0.04–0.17) and rapidly after 2010 (0.34/year, 95% CI 0.18–0.49).
The mortality gap between individuals with bipolar disorder and schizophrenia, and the general population is widening.
Persistent pain is common and inadequately treated in cancer patients. Behavioral pain interventions are a recommended part of multimodal pain treatments, but they are underused in clinical care due to barriers such as a lack of the resources needed to deliver them in person and difficulties coordinating their use with clinical care. Pain coping skills training (PCST) is an evidence-based behavioral pain intervention traditionally delivered in person. Delivering this training via the web would increase access to it by addressing barriers that currently limit its use. We conducted a patient pilot study of an 8-week web-based PCST program to determine the acceptability of this approach to patients and the program features needed to meet their needs. Focus groups with healthcare providers identified strategies for coordinating the use of web-based PCST in clinical care.
Participants included 7 adults with bone pain due to multiple myeloma or metastasized breast or prostate cancer and 12 healthcare providers (4 physicians and 8 advanced practice providers) who treat cancer-related bone pain. Patients completed web-based PCST at home and then took part in an in-depth qualitative interview. Providers attended focus groups led by a trained moderator. Qualitative analyses identified themes in the patient and provider data.
Patients reported strongly favorable responses to web-based PCST and described emotional and physical benefits. They offered suggestions for adapting the approach to better fit their needs and to overcome barriers to completion. Focus groups indicated a need to familiarize healthcare providers with PCST and to address concerns about overburdening patients. Providers would recommend the program to patients they felt could benefit. They suggested applying a broad definition of cancer pain and having various types of providers help coordinate program its use with clinical care.
Significance of results:
Web-based PCST was acceptable to patients and providers. Our findings suggest that patients could benefit from this approach, especially if patient and provider barriers are addressed.
Congenital or early life infection with Toxoplasma gondii has been implicated in schizophrenia aetiology. Childhood cat ownership has been hypothesized as an intermediary marker of T. gondii infection and, by proxy, as a risk factor for later psychosis. Evidence supporting this hypothesis is, however, limited.
We used birth cohort data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate whether cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews. We used logistic regression to examine associations between cat ownership and PEs, adjusting for several sociodemographic and socioeconomic factors, household characteristics and dog ownership. Missing data were handled via multiple imputation.
Cat ownership during pregnancy was not associated with PEs at age 13 years [adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 0.97–1.35] or 18 years (OR 1.08, 95% CI 0.86–1.35). Initial univariable evidence that cat ownership at ages 4 and 10 years was associated with PEs at age 13 years did not persist after multivariable adjustment (4 years: OR 1.18, 95% CI 0.94–1.48; 10 years: OR 1.12, 95% CI 0.92–1.36). There was no evidence that childhood cat ownership was associated with PEs at age 18 years.
While pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs.
Measuring and mitigating methane (CH4) emissions from livestock is of increasing importance for the environment and for policy making. Potentially, the most sustainable way of reducing enteric CH4 emission from ruminants is through the estimation of genomic breeding values to facilitate genetic selection. There is potential for adopting genetic selection and in the future genomic selection, for reduced CH4 emissions from ruminants. From this review it has been observed that both CH4 emissions and production (g/day) are a heritable and repeatable trait. CH4 emissions are strongly related to feed intake both in the short term (minutes to several hours) and over the medium term (days). When measured over the medium term, CH4 yield (MY, g CH4/kg dry matter intake) is a heritable and repeatable trait albeit with less genetic variation than for CH4 emissions. CH4 emissions of individual animals are moderately repeatable across diets, and across feeding levels, when measured in respiration chambers. Repeatability is lower when short term measurements are used, possibly due to variation in time and amount of feed ingested prior to the measurement. However, while repeated measurements add value; it is preferable the measures be separated by at least 3 to 14 days. This temporal separation of measurements needs to be investigated further. Given the above issue can be resolved, short term (over minutes to hours) measurements of CH4 emissions show promise, especially on systems where animals are fed ad libitum and frequency of meals is high. However, we believe that for short-term measurements to be useful for genetic evaluation, a number (between 3 and 20) of measurements will be required over an extended period of time (weeks to months). There are opportunities for using short-term measurements in standardised feeding situations such as breath ‘sniffers’ attached to milking parlours or total mixed ration feeding bins, to measure CH4. Genomic selection has the potential to reduce both CH4 emissions and MY, but measurements on thousands of individuals will be required. This includes the need for combined resources across countries in an international effort, emphasising the need to acknowledge the impact of animal and production systems on measurement of the CH4 trait during design of experiments.
Fe deficiency anaemia during early pregnancy has been linked with low birth
weight and preterm birth. However, this evidence comes mostly from studies
measuring Hb levels rather than specific measures of Fe deficiency. The present
study aimed to examine the association between maternal Fe status during the
first trimester of pregnancy, as assessed by serum ferritin, transferrin
receptor and their ratio, with size at birth and preterm birth. In the Baby VIP
(Baby's Vascular health and Iron in Pregnancy) study, we recruited 362
infants and their mothers after delivery in Leeds, UK. Biomarkers were measured
in maternal serum samples previously obtained in the first trimester of
pregnancy. The cohort included sixty-four (18 %) small for gestational
age (SGA) babies. Thirty-three babies were born preterm (9 %; between 34
and 37 weeks). First trimester maternal Fe depletion was associated with a
higher risk of SGA (adjusted OR 2·2, 95 % CI 1·1,
4·1). This relationship was attenuated when including early pregnancy Hb
in the model, suggesting it as a mediator (adjusted OR 1·6, 95 %
CI 0·8, 3·2). For every 10 g/l increase in maternal Hb
level in the first half of pregnancy the risk of SGA was reduced by 30 %
(adjusted 95 % CI 0, 40 %); levels below 110 g/l were
associated with a 3-fold increase in the risk of SGA (95 % CI 1·0,
9·0). There was no evidence of association between maternal Fe depletion
and preterm birth (adjusted OR 1·5, 95 % 0·6, 3·8).
The present study shows that depleted Fe stores in early pregnancy are
associated with higher risk of SGA.
Feed is a major component of variable costs associated with dairy systems and is therefore an important consideration for breeding objectives. As a result, measures of feed efficiency are becoming popular traits for genetic analyses. Already, several countries account for feed efficiency in their breeding objectives by approximating the amount of energy required for milk production, maintenance, etc. However, variation in actual feed intake is currently not captured in dairy selection objectives, although this could be possible by evaluating traits such as residual feed intake (RFI), defined as the difference between actual and predicted feed (or energy) intake. As feed intake is expensive to accurately measure on large numbers of cows, phenotypes derived from it are obvious candidates for genomic selection provided that: (1) the trait is heritable; (2) the reliability of genomic predictions are acceptable to those using the breeding values; and (3) if breeding values are estimated for heifers, rather than cows then the heifer and cow traits need to be correlated. The accuracy of genomic prediction of dry matter intake (DMI) and RFI has been estimated to be around 0.4 in beef and dairy cattle studies. There are opportunities to increase the accuracy of prediction, for example, pooling data from three research herds (in Australia and Europe) has been shown to increase the accuracy of genomic prediction of DMI from 0.33 within country to 0.35 using a three-country reference population. Before including RFI as a selection objective, genetic correlations with other traits need to be estimated. Weak unfavourable genetic correlations between RFI and fertility have been published. This could be because RFI is mathematically similar to the calculation of energy balance and failure to account for mobilisation of body reserves correctly may result in selection for a trait that is similar to selecting for reduced (or negative) energy balance. So, if RFI is to become a selection objective, then including it in an overall multi-trait selection index where the breeding objective is net profit is sensible, as this would allow genetic correlations with other traits to be properly accounted for. If genetic parameters are accurately estimated then RFI is a logical breeding objective. If there is uncertainty in these, then DMI may be preferable.
Serum samples were obtained from 281 heifers vaccinated with Brucella abortus strain 19, and from 50 heifers that had received two injections of killed B. abortus strain 45/20 adjuvant (K45/20A) vaccine. The serological response measured by the brucellosis radioimmunoassay (RIA) was compared with responses measured by other tests.
The serological responses of cattle during the first weeks after strain 19 vaccination were found to give little guide to the frequency of persistent reactions.
In the case of strain 19, persistent reactions were considered to be those occurring 12 or more months after vaccination. In heifers vaccinated at the recommended age, small numbers of persistent reactions were given by the RIA (four in 374 sera), the complement fixation test using warm fixation (CFTW) (six in 383) and cold fixation (one in 185), the serum agglutination test (two in 222) and the indirect haemolysis test (IHLT) (two in 369). The Rose Bengal plate test gave 74 persistent reactions in 374 sera.
Five of the 50 heifers gave particularly prolonged responses to K45/20A vaccine. In these animals the RIA and IHLT remained positive for longer than the CFTW.
The patterns of linkage disequilibrium (LD) between dense polymorphic markers are shaped by the ancestral population history. It is therefore possible to use multilocus predictors of LD to infer past population history and to infer sharing of identical alleles in quantitative trait locus (QTL) studies. We develop a multilocus predictor of LD for pairs of haplotypes, which we term haplotype homozygosity (HHn): the probability that any two haplotypes share a given number of n adjacent identical markers or ‘runs of homozygosity’. Our method, based on simplified coalescence theory, accounts for recombination and mutation. We compare our HHn predictions, with HHn in simulated populations and with two published predictors of HHn. Our method performs consistently better across a range of population parameters, including populations with a severe bottleneck followed by expansion, compared to two published methods. We demonstrate that we can predict the pattern of HHn observed in dense single nucleotide polymorphisms (SNPs) genotyped in a cattle population, given appropriate historical changes in population size. Our method is practical for use with very large numbers of individuals and dense genome wide polymorphic DNA data. It has potential applications in inferring ancestral population history and QTL mapping studies.
We describe our efforts to control the grain boundary alignment in polycrystalline thin films of silicon by using a biaxially textured template layer of CaF2 for photovoltaic device applications. We have chosen CaF2 as a candidate material due to its close lattice match with silicon and its suitability as an ion beam assisted deposition (IBAD) material. We show that the CaF2 aligns biaxially at a thickness of ~10 nm and, with the addition of an epitaxial CaF2 layer, has an in-plane texture of ~15°. Deposition of a subsequent layer of Si aligns on the template layer with an in-plane texture of 10.8°. The additional improvement of in-plane texture is similar to the behavior observed in more fully characterized IBAD materials systems. A germanium buffer layer is used to assist in the epitaxial deposition of Si on CaF2 template layers and single crystal substrates. These experiments confirm that an IBAD template can be used to biaxially orient polycrystalline Si.
A number of farmed species are characterized by breeding populations of large full-sib families, including aquaculture species and outcrossing plant species. Whole genome association studies in such species must account for stratification arising from the full-sib family structure to avoid high rates of false discovery. Here, we demonstrate the value of selective genotyping strategies which balance the contribution of families across high and low phenotypes to greatly reduce rates of false discovery with a minimal effect on power.
This case report describes a patient with reportedly new onset of tics, beginning at 21 years of age, in the context of posttraumatic stress disorder (PTSD) and comorbid alcohol abuse, with no known head injury. The setting is an American Society of Addiction Medicine intensive outpatient substance abuse rehabilitation program in an United States Army Medical Center. The patient is a 22-year-old male diagnosed with alcohol abuse and delayed PTSD who presented to the program's medical officer due to insomnia. We discovered he had a reportedly new ocular tic of ∼9 months duration, which he claimed developed at 21 years of age soon after returning from 1 year of combat duty. The patient was thoroughly evaluated, and we surmised the tic was a symptom of PTSD. After achieving full remission from alcohol, the tic persisted. However, as his PTSD symptoms remitted, so did his tic symptoms. At 6-month follow-up, the patient reported he was essentially free from PTSD symptoms, and his tic was significantly reduced.
Dense marker genotypes allow the construction of the realized relationship matrix between individuals, with elements the realized proportion of the genome that is identical by descent (IBD) between pairs of individuals. In this paper, we demonstrate that by replacing the average relationship matrix derived from pedigree with the realized relationship matrix in best linear unbiased prediction (BLUP) of breeding values, the accuracy of the breeding values can be substantially increased, especially for individuals with no phenotype of their own. We further demonstrate that this method of predicting breeding values is exactly equivalent to the genomic selection methodology where the effects of quantitative trait loci (QTLs) contributing to variation in the trait are assumed to be normally distributed. The accuracy of breeding values predicted using the realized relationship matrix in the BLUP equations can be deterministically predicted for known family relationships, for example half sibs. The deterministic method uses the effective number of independently segregating loci controlling the phenotype that depends on the type of family relationship and the length of the genome. The accuracy of predicted breeding values depends on this number of effective loci, the family relationship and the number of phenotypic records. The deterministic prediction demonstrates that the accuracy of breeding values can approach unity if enough relatives are genotyped and phenotyped. For example, when 1000 full sibs per family were genotyped and phenotyped, and the heritability of the trait was 0·5, the reliability of predicted genomic breeding values (GEBVs) for individuals in the same full sib family without phenotypes was 0·82. These results were verified by simulation. A deterministic prediction was also derived for random mating populations, where the effective population size is the key parameter determining the effective number of independently segregating loci. If the effective population size is large, a very large number of individuals must be genotyped and phenotyped in order to accurately predict breeding values for unphenotyped individuals from the same population. If the heritability of the trait is 0·3, and Ne=1000, approximately 5750 individuals with genotypes and phenotypes are required in order to predict GEBVs of un-phenotyped individuals in the same population with an accuracy of 0·7.
The relation between impurity content in Solar Grade Silicon (SGS) and solar cell quality is the subject of intensive research. The PV industry has developed around the use of silicon made by the Siemens process for the semiconductor industry, with impurity levels typically in the parts per billion by weight (ppbw) range. There is a growing consensus that SGS with impurities in the parts per million range (ppmw) can be obtained cost effectively from Metallurgical Grade Silicon (MGS) and used to yield solar cells with comparable performance (see for example ‘Beneficial Effects of Dopant Compensation on Carrier Lifetime in Upgraded Metallurgical Silicon’ by S. Dubois et al. in the 23rd European Photovoltaic Solar Energy Conference, Valencia, September, 2008). This provides insight on the success encountered by Timminco, an early SGS market entrant, in commercializing silicon material with [P] levels of the order of 2 ppmw.
We have successfully reduced P to about 2 ppmw, a level that appears acceptable for solar cell fabrication, by application of a novel unidirectional solidification (UDS) technique at a 50% material yield. This is important as UDS, by its nature, implies a loss of silicon, while little or no silicon is lost in B reduction, partially achieved in this furnace using a glass slagging process. Figure 1 shows [P] data from 16 UDS runs on samples taken from the melt, before and after UDS, and a solid sample taken from the silicon frozen on the cold silicon collection surface. The error bars represent a standard 20% error value. We note that the average values of [P] in the molten silicon samples increase from 11.9 ppmw before UDS to 15.9 ppmw after UDS. The average value of [P] in the solid silicon sample is 4.9 ppmw.
The average value of the solid silicon, 4.9 ppmw P, taken with the average value of the starting silicon, 11.9 ppmw P, demonstrates an effective refining ratio of 0.41, even at a 50% solid fraction. Performing a second UDS on silicon obtained from runs in Figure 1, yields [P] around 2 ppmw (Figure 2).In addition to P and B reduction, in this paper we also discuss the hardware designed to implement this process in commercial production in volumes exceeding 4,000 MT per year. MB Scientific, the original process developer, and NC Consulting, an engineering company, have developed a plant design that can produce SGS at an estimated cost that will allow for profitable large scale production, and have joined in a new company, Silicon Forge, to commercialize the large-scale production technology.