ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group.

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays. For patients with advanced cancer, validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, and may be used in routine clinical practice, provided the limitations of the assays are taken into account. Tissue-based testing remains the preferred test for many cancer patients, due to limitations of ctDNA assays detecting fusion events and copy number changes, although ctDNA assays may be routinely used when faster results will be clinically important, or when tissue biopsies are not possible or inappropriate. Reflex tumour testing should be considered following a non-informative ctDNA result, due to false-negative results with ctDNA testing. In patients treated for early-stage cancers, detection of molecular residual disease or molecular relapse, has high evidence of clinical validity in anticipating future relapse in many cancers. Molecular residual disease/molecular relapse detection cannot be recommended in routine clinical practice, as currently there is no evidence for clinical utility in directing treatment. Additional potential applications of ctDNA assays, under research development and not recommended for routine practice, include identifying patients not responding to therapy with early dynamic changes in ctDNA levels, monitoring therapy for the development of resistance mutations before clinical progression, and in screening asymptomatic people for cancer. Recommendations for reporting of results, future development of ctDNA assays and future clinical research are made.

Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" products.

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix.

PURPOSE: Our purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components. METHODS: Expression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS. RESULTS: Approximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, ß-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells. CONCLUSIONS: LN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.

A Controlled Randomized Preliminary Trial of a Modified Dissonance-Based Eating Disorder Intervention Program.

OBJECTIVE: We conducted a controlled randomized preliminary trial of a modified dissonance-based eating disorder program (n = 24) compared to an assessment-only control condition (n = 23) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 47) with clinical (n = 22) and subclinical (n = 25) eating disorder symptoms. METHOD: The traditional content of the Body Project, a dissonance-based eating disorder prevention program, was modified to include verbal, written, and behavioral exercises designed to dissuade self-objectification and maladaptive social comparison. Women with clinical and subclinical symptoms were included in the target audience to investigate both the treatment and the indicated prevention utility of the modified dissonance program. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, and eating disorder symptoms were evaluated in the control and the modified dissonance condition at baseline, postintervention, and 2-month follow-up. RESULTS: We predicted a statistically significant 2 (condition: control, modified dissonance) x 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial multivariate analyses of variance results. Results confirmed this hypothesis. Eating disorder risk factors and symptoms decreased significantly among participants in the modified dissonance condition at postintervention and 2-month follow-up compared to baseline; symptom improvement was greater among participants in the modified compared to the control condition. A secondary analysis indicated symptom improvement did not vary as a function of symptom status (clinical, subclinical), suggesting the program is efficacious in both indicated prevention and treatment applications. CONCLUSION: Results provide preliminary support for the modified dissonance program.

A quantitative LC/MS method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies.

Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC-ESI-MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3%, respectively, at the mean urinary concentration level, while method accuracy was between -16.2 and 8.0% across the linear concentration range of 22-1,111 ng mL(-1). Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 µmol mmol(-1) of creatinine, and for male subjects, it was 2.1 µmol mmol(-1) of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.

Patient participation in care and rehabilitation from the perspective of patients with spinal cord injury.

STUDY DESIGN: Qualitative method, semi-structured interviews. OBJECTIVES: The aim of the study was to explore the meaning of patient participation in care and rehabilitation from the perspective of patients with spinal cord injury (SCI). SETTING: Post discharge community setting. METHODS: Semi-structured interviews were performed with 10 persons with SCI representing different ages, gender and levels of injury. All interviews were conducted individually and lasted 40-120 min. The interviews were verbally transcribed and the data were analyzed by means of content analysis. RESULTS: All informants stressed the importance of patient participation as a necessary prerequisite for successful care and rehabilitation, but emphasized that participation must be tailored to each patient's own preferences, capacities and needs. They also underscored that the staff should be sensitive and responsive to the fact that desired levels and kinds of participation may vary from patient to patient, as well as for the same patient during the course of the rehabilitation. Five themes reflecting central aspects of participation emerged: respect and integrity, planning and decision-making, information and knowledge, motivation and encouragement, and involvement of family. CONCLUSIONS: Patient participation is a critical component of successful SCI rehabilitation and must be facilitated, promoted and tailored to each patient by the staff. Based on the finding from this study a questionnaire has been developed for assessing patient experiences of five domains of participation in rehabilitation to serve as a tool to help in evaluating provided care and in identifying patients' preferences for participation.

Patient Participation in Rehabilitation Questionnaire (PPRQ)-development and psychometric evaluation.

STUDY DESIGN: A cross-sectional postal questionnaire study. OBJECTIVES: The aim of the study was to evaluate selected psychometric properties of a draft version of the Patient Participation in Rehabilitation Questionnaire (PPRQ) measuring patients' experiences of participation in care and rehabilitation. SETTING: Sweden. METHODS: On the basis of previous qualitative analyses of patient interview data, a 32-item questionnaire covering five domains of participation was developed and sent to 268 persons with spinal cord injury, aged 18-80 years and injured 1-12 years previously. In total, 141 (51%) evaluable questionnaires were returned. Multi-trait analysis was used to assess scaling assumptions by testing item convergent and discriminant validity and internal consistency reliability (Cronbach's α) associated with the hypothesized item-scale structure of the questionnaire. RESULT: Nine items failed to meet scaling assumptions and were omitted. Scaling assumptions were thereafter substantiated for the scales: 'respect and integrity' (6 items); 'planning and decision-making' (4 items); 'information and knowledge' (4 items); 'motivation and encouragement' (5 items); and 'involvement of family' (4 items). Item-scale correlations ranged from 0.67 to 0.85 and most items correlated higher or significantly higher with their hypothesized scale than with other scales. Cronbach's α was 0.89 for all scales. CONCLUSION: The PPRQ appears to adequately assess central aspects of participation in care and rehabilitation from the perspective of patients with spinal cord injury. Further studies using larger samples will be undertaken to confirm the scale structure as well as the sensitivity and responsiveness of the questionnaire.

Review: Nutrient and energy supply in monogastric food producing animals with reduced environmental and climatic footprint and improved gut health.

With more efficient utilisation of dietary nutrients and energy, diversified production systems, modifications of diet composition with respect to feedstuffs included and the use of free amino acids, the negative impact of animal food production on the environment and climate can be reduced. Accurate requirements for nutrients and energy for animals with differing physiological needs, and the use of robust and accurate feed evaluation systems are key for more efficient feed utilisation. Data on CP and amino acid requirements in pigs and poultry indicate that it should be possible to implement indispensable amino acid-balanced diets with low- or reduced-protein content without any reduction in animal performance. Potential feed resources, not competing with human food security, can be derived from the traditional food- and agroindustry, such as various waste streams and co-products of different origins. In addition, novel feedstuffs emerging from aquaculture, biotechnology and innovative new technologies may have potential to provide the lack of indispensable amino acids in organic animal food production. High fibre content is a nutritional limitation of using waste streams and co-products as feed for monogastric animals as it is associated with decreased nutrient digestibility and reduced dietary energy values. However, minimum levels of dietary fibre are needed to maintain the normal physiological function of the gastro-intestinal tract. Moreover, there may be positive effects of fibre in the diet such as improved gut health, increased satiety, and an overall improvement of behaviour and well-being.

Chemical Characterization and Water Holding Capacity of Fibre-rich Feedstuffs Used for Pigs in Vietnam.

During two years, four samples per year were collected in Vietnam from rice bran, cassava residue, brewer's grain, tofu residue, soybean meal, coconut cake, sweet potato vines and water spinach for chemical analysis and assessment of water holding capacity (WHC). The selected feedstuffs represent fibre-rich plant sources and agro-industry co-products commonly used in pig feeding in Vietnam. The content (g/kg DM) of crude protein (CP), ether extract (EE) and non-starch polysaccharides (NSP) varied between feedstuffs and ranged from 21 to 506 for CP, from 14 to 118 for EE and from 197 to 572 for NSP. Cassava residue had a high starch content of 563 g/kg DM, while sweet potato vines, water spinach, coconut cake and soybean meal had a high content of sugars (63-71 g/kg DM). The content of individual neutral sugars varied between feed ingredients, with the highest content of arabinose, galactose and glucose in tofu residue, the highest content of xylose in brewer's grain and the highest content of mannose in coconut cake. The content of uronic acid was high for cassava residue, tofu residue, sweet potato vines and water spinach (57-88 g/kg DM). The content of soluble non-cellulosic polysaccharides (S-NCP) was positively correlated (r(2) = 0.82) to the WHC. The content (g/kg DM) of CP, NDF, neutral sugars, total NSP, total NCP, S-NCP and total dietary fibre in tofu residue, water spinach and coconut cake varied (p<0.05) between years. In conclusion, diet formulation to pigs can be improved if the variation in chemical composition of the fibre fraction and in WHC between potential feed ingredients is taken into account.

Effect of Fibre Level and Fibre Source on Gut Morphology and Micro-environment in Local (Mong Cai) and Exotic (Landrace×Yorkshire) Pigs.

The effect of genotype, fibre level and fibre source on gut morphology, environment and microflora was studied using 18 Mong Cai (MC) and 18 Landrace×Yorkshire (LY) pigs, aged around 60 d. The diets were based on maize, rice bran, soybean meal, fish meal and soybean oil, and cassava residue (CR) or brewer's grain (BG) as fibrous ingredient sources in the high-fibre diets (HF). A low-fibre diet (LF), containing around 200 g NDF/kg dry matter (DM), was formulated without CR and BG as feed ingredients. The HF diets (HF-CR and HF-BG) were formulated to contain around 270 g NDF/kg DM. The experiment was arranged according to a 2×3 factorial completely randomized design with six replications, and lasted 30 d. Crypt density in ileum was lowest (p<0.05) and villus height in jejunum and ileum were the greatest (p<0.05) in pigs fed diet HF-BG. Villus width in ileum was greatest in pigs fed diets HF-CR and HF-BG (p<0.05). Lactic acid bacteria (LAB) counts in stomach were greatest (p<0.05) and E. coli counts in ileum and colon were lowest (p<0.05) in pigs fed diet HF-CR. The concentration of total organic acids in ileum, caecum and colon were greatest (p<0.05), and pH in ileum and colon were lowest (p<0.05) in pigs fed diet HF-CR. Crypt density in ileum was lowest, and villus height in ileum and villus width in jejunum and ileum was greatest in LY pigs (p<0.05). LAB counts in stomach and ileum were greatest, and E. coli counts in ileum were lowest in MC pigs (p<0.05). The concentration of total organic acids in ileum, caecum and colon were greatest (p<0.05) and pH lowest (p<0.05) in MC pigs.

Growth performance, digestibility, and gut development of broiler chickens on diets with inclusion of chicory (Cichorium intybus L.).

A total of 256 broiler chickens (1 d old) were used in a 32-d growth trial to study the effects of chicory (Cichorium intybus L.) forage and root inclusion on growth performance, digestibility, and gut development. The chicory forage originated from 2 harvests (June and September) and was included at 60 and 120 g/kg. The chicory root was included alone at 60 g/kg or together with chicory forage, from both harvests, in equal amounts (60 g/kg). The cereal-based control diet and 7 experimental diets were fed to each of 4 pens of chickens (8 chickens/pen). A higher BW gain and lower feed conversion ratio were found at 13 d of age in chickens fed the 60 g/kg chicory forage diet (P ≤ 0.05), whereas performance did not differ between the control and 60 g/kg chicory root diets. In contrast, a lower performance and digestibility of DM, organic matter, and AME as well as a thinner cecal mucosa layer were found for the 120 g/kg chicory forage diet (P ≤ 0.05). No diet effects on organ parameters or on pH of cecum digesta were detected. The soluble nonstarch polysaccharides fractions of chicory forage did not have any major negative effects on performance and gut development, and chicory forage from the September harvest was seen to have a higher nutritional value than that from the June harvest. Thus, results from the current study suggest that chicory forage is a potentially useful fiber-rich feed ingredient with high palatability for broiler chickens.

Healthy Aging Requires a Healthy Home Care Workforce: the Occupational Safety and Health of Home Care Aides.

PURPOSE OF REVIEW: To identify important home care (HC) aide occupational safety and health (OSH) hazards and examine how addressing these can improve aide health and the delivery of HC services overall. Specifically, this review seeks to answer: Why is HC aide OSH important? What are the most significant OSH challenges? How can improving HC aide OSH also improve the safety and health of their clients? What implications do the findings have for future research? RECENT FINDINGS: HC is one of the fastest growing US industries. Aides comprise its largest workforce and are increasingly needed to care for the rapidly aging population. There is an aide shortage due in part to instabilities in HC work organization and to serious job-specific hazards, resulting in aides losing work time. Recent social, economic, and technological factors are rapidly changing the nature of HC work, creating OSH hazards similar to those found in nursing homes. At the same time, aides are experiencing social and economic inequities that increase their vulnerability to OSH hazards. These hazards are also a burden on employers who are challenged to recruit, retain, and train aides. OSH injuries and illness interrupt the continuity of care delivery to clients. Many OSH hazards also put HC clients and families at risk. A new framework and methodologies are needed to assess aide and client safety together in order to guide future HC research, policies, and practices. Government, industry, and labor commitment is needed to fund and coordinate a comprehensive, multidisciplinary research program.

Impact of feeding level on digestibility of a haylage-only diet in Icelandic horses.

Eight mature Icelandic geldings were used in an experiment arranged as a change-over design to evaluate the effect of feeding level on the digestibility of a high-energy haylage-only diet. The horses were fed a low feeding level 10.7 g dry matter (DM)/kg body weight (BW) (maintenance) and a high feeding level 18.1 g DM/kg BW (1.5 × maintenance) during two 23 days experimental periods. Total collection of faeces was performed for 6 days at the end of each period to determine the coefficient of total tract apparent digestibility (CTTAD). The CTTAD for DM, organic matter, neutral detergent fibre (NDF), acid detergent fibre and energy was higher in horses fed at the low level of feed intake, while feeding level did not affect the CTTAD of crude protein. The largest difference in CTTAD between feeding levels was found for NDF. The content (/kg DM) of digestible energy in the haylage was 11.3 MJ at the low level of feed intake and 10.6 MJ at the high level of feed intake. It can be concluded that feeding level has a large impact on the digestibility and energy value of early cut haylage in Icelandic horses.

Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles.

BACKGROUND: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. OBJECTIVE: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. METHODS: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, alpha-enolase peptide-1 and the C1-epitope of type II collagen (C1(III)). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. RESULTS: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated alpha-enolase peptide-1 and citrullinated C1(III). These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles. CONCLUSIONS: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.

Changes in faecal bacteria associated with concentrate and forage-only diets fed to horses in training.

REASONS FOR PERFORMING STUDY: Diets rich in readily fermentable carbohydrates, fed traditionally to meet the increased energy requirements of the performance horse, are associated with a number of gastrointestinal disorders that involve disturbances in the intestinal microbiota, however, these changes are poorly understood. OBJECTIVES: With the long-term objective of improving intestinal health and to increase understanding of the relationship between diet and microbiota, the effect of feeding Standardbred horses a high-energy forage-only (F) diet was studied compared to a more traditional forage-concentrate (C) diet on faecal microbiota. METHODS: Diets were fed in a cross-over design to 6 mature geldings on a scheduled training regime, both periods consisting of 29 days. DNA was extracted from faecal samples collected at 4 time points from each period, bacterial 16S rRNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing. Faecal pH and cultivable lactic acid bacteria (LAB) and enterobacteria were also assessed on the final collection day of each period. RESULTS: Diet F resulted in a microbial composition that was more stable between sampling periods and had lower counts (P < 0.05) of cultivable LAB and specifically members of the Streptococcus bovislequinus complex. Motile and swarming Lactobacillus ruminis was present in all horses on diet C and not in horses on diet F. Diet C also resulted in the increase (P < 0.05) in members of Clostridiaceae cluster III and a concomitant reduction (P < 0.05) in an unknown group of Bacteroidales. CONCLUSIONS AND POTENTIAL RELEVANCE: The greater microbial stability and reduction in LAB and members of the Streptococcus bovis/equinus complex on diet F indicate an opportunity to develop feeding strategies that support equine health and welfare. Novel changes identified in the faecal microbiota that resulted from carbohydrate inclusion merit further investigation.

Comparison of total tract digestibility, development of visceral organs and digestive tract of Mong cai and Yorkshire x Landrace piglets fed diets with different fibre sources.

The aim of the study was to evaluate the effects of piglet age and dietary fibre source on the development of visceral organs and the gastrointestinal tract (GIT), and on growth performance and total tract apparent digestibility (TTAD) in local [pure-breed Mong cai (MC)] and exotic [Landrace x Yorkshire (LY)] piglets. The experimental diets contained different fibre sources: C (basal diet), RB (basal diet + rice bran), SPVM (basal diet + sweet potato vine meal) and CReM (basal diet + cassava residue meal). The neutral detergent fibre (NDF) content in diet C and the fibrous diets was 8.8% and 17.1%-17.7% respectively (dry matter basis). Collection of faecal samples to determine TTAD was carried out for five consecutive days before the experiment was finished (63 days). The piglets were killed at the age of 10 days (before being given the same solid feed), 30 days (weaning, 20 days after solid feed introduced) and 63 days (33 days after being given the different fibrous diets) when the length of intestinal segments, weight of organs (liver, heart, kidneys) and empty weight of the GIT (stomach, small intestine, caecum and colon + rectum) were measured. As the age of animals increased, the relative weight of organs and the length of intestines (expressed on a mass-specific basis) decreased (p < 0.05), and the weight of GIT increased (p < 0.001). The piglets fed fibrous diets had heavier GIT than those fed diet C with the highest values in CReM (p < 0.05). The colon + rectum length was not significantly different among C, RB and SPVM, but was shorter than in CReM (p < 0.05). Coefficient of total tract apparent digestibility (CTTAD) of nutrients in the fibrous diets was lower than in C (p < 0.01). Average daily gain (ADG) and feed conversion ratio (FCR) in C, RB and CReM were not different and were better than in SPVM (p < 0.01). There were no significant differences in the weights of organs between the two breeds at day 10, 30 and 63 (p > 0.05). The weight and length of GIT were not significantly different between the two breeds at day 10 and day 30, but were greater for MC at day 63. The caecum and colon + rectum at 10 and 30 days were longer in MC than in LY (p < 0.001). The relative development of GIT post-weaning was higher than pre-weaning, the difference being most apparent in MC. As a result at 63 days, MC had heavier visceral organs and GIT, and longer intestines on fibrous diets than LY (p < 0.05). The MC at 63 days had higher CTTAD of organic matter, gross energy, crude fibre and NDF (p < 0.001) and ether extract and crude protein (p < 0.05), but lower ADG and poorer FCR than LY (p < 0.001). It can be concluded that the GIT of the MC piglets developed more rapidly than LY when they were introduced to solid feed, and that the difference was more marked on the fibrous diets and after weaning, which resulted in higher total tract digestibility of nutrients in MC compared with LY. Cassava residue meal was better digested than RB and SPVM, and supported higher live weight gains.

Efficiency of Colorectal Cancer Surveillance in Patients with Ulcerative Colitis: 38 Years' Experience in a Patient Cohort from a Defined Population Area.

BACKGROUND AND AIMS: Ulcerative colitis increases the risk of developing colorectal cancer. Colonoscopic surveillance is recommended although there are no randomized trials evaluating the efficacy of such a strategy. This study is an update of earlier studies from an ongoing colonoscopic surveillance program. MATERIAL AND METHODS: All patients with ulcerative colitis were invited to the surveillance program that started in 1977 at Örnsköldsvik Hospital, located in the northern part of Sweden. Five principal endoscopists performed the colonoscopies and harvested mucosal sampling for histopathological evaluation. Some 323 patients from the defined catchment area were studied from 1977 to 2014. At the end of the study period, 130 patients, including those operated on, had had total colitis for more than 10 years. RESULTS: In total, 1481 colonoscopies were performed on 323 patients during the study period without any major complications. In all, 10 cases of colorectal cancer were diagnosed in 9 patients, of whom 1 died from colorectal cancer. The cumulative incidence of colorectal cancer was 1.4% at 10 years, 2.0% at 20 years, 3.0% at 30 years, and 9.4% at 40 years of disease duration, respectively. The standardized colorectal cancer incidence ratio was 3.01 (95% confidence interval: 1.42-5.91). Major surgery was performed on 65 patients; for 20 of these, the indication for surgery was dysplasia or colorectal cancer. Panproctocolectomy was performed in 43 patients. CONCLUSION: This study supports that colonoscopic surveillance is a safe and effective long-term measure to detect dysplasia and progression to cancer. The low numbers of colorectal cancer-related deaths in our study suggest that early detection of neoplasia and adequate surgical intervention within a surveillance program may reduce colorectal cancer mortality in ulcerative colitis patients.

Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value<0.05; concordance index >0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

Prostate cancer screening in men aged 50 to 69 years (STHLM3): A prospective population-based diagnostic study. Grönberg H, Adolfsson J, Aly M, Nordström T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M.Lancet Oncol. 2015 Dec;16(16):1667-76. [Epub 2015 Nov 10]. doi: 10.1016/S1470-2045(15)00361-7.

BACKGROUND: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. METHODS: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406. FINDINGS: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies. INTERPRETATION: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. FUNDING: Stockholm County Council (Stockholms Läns Landsting).