Inflated Uncertainty in Multimodel-Based Regional Climate Projections.

Multimodel ensembles are widely analyzed to estimate the range of future regional climate change projections. For an ensemble of climate models, the result is often portrayed by showing maps of the geographical distribution of the multimodel mean results and associated uncertainties represented by model spread at the grid point scale. Here we use a set of CMIP5 models to show that presenting statistics this way results in an overestimation of the projected range leading to physically implausible patterns of change on global but also on regional scales. We point out that similar inconsistencies occur in impact analyses relying on multimodel information extracted using statistics at the regional scale, for example, when a subset of CMIP models is selected to represent regional model spread. Consequently, the risk of unwanted impacts may be overestimated at larger scales as climate change impacts will never be realized as the worst (or best) case everywhere.

Prevalence of neuropathic pain according to the IASP grading system in patients with chronic non-malignant pain.

OBJECTIVE: The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. SETTING: A Multidisciplinary Pain Center. SUBJECTS: One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. METHODS: Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. RESULTS: According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. CONCLUSIONS: According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire.

Study protocol: Rehabilitation including Social and Physical activity and Education in Children and Teenagers with Cancer (RESPECT).

BACKGROUND: During cancer treatment children have reduced contact with their social network of friends, and have limited participation in education, sports, and leisure activities. During and following cancer treatment, children describe school related problems, reduced physical fitness, and problems related to interaction with peers. METHODS/DESIGN: The RESPECT study is a nationwide population-based prospective, controlled, mixed-methods intervention study looking at children aged 6-18 years newly diagnosed with cancer in eastern Denmark (n=120) and a matched control group in western Denmark (n=120). RESPECT includes Danish-speaking children diagnosed with cancer and treated at pediatric oncology units in Denmark. Primary endpoints are the level of educational achievement one year after the cessation of first-line cancer therapy, and the value of VO2max one year after the cessation of first-line cancer therapy. Secondary endpoints are quality of life measured by validated questionnaires and interviews, and physical performance. RESPECT includes a multimodal intervention program, including ambassador-facilitated educational, physical, and social interventions. The educational intervention includes an educational program aimed at the child with cancer, the child's schoolteachers and classmates, and the child's parents. Children with cancer will each have two ambassadors assigned from their class. The ambassadors visit the child with cancer at the hospital at alternating 2-week intervals and participate in the intervention program. The physical and social intervention examines the effect of early, structured, individualized, and continuous physical activity from diagnosis throughout the treatment period. The patients are tested at diagnosis, at 3 and 6 months after diagnosis, and one year after the cessation of treatment. The study is powered to quantify the impact of the combined educational, physical, and social intervention programs. DISCUSSION: RESPECT is the first population-based study to examine the effect of early rehabilitation for children with cancer, and to use healthy classmates as ambassadors to facilitate the normalization of social life in the hospital. For children with cancer, RESPECT contributes to expanding knowledge on rehabilitation that can also facilitate rehabilitation of other children undergoing hospitalization for long-term illness. TRIAL REGISTRATION: Clinical Trials.gov: file. NCT01772849 and NCT01772862.

Hospital-based home care for children with cancer: feasibility and psychosocial impact on children and their families.

BACKGROUND: To assess the feasibility and psychosocial impact of a hospital-based home care (HBHC) program for children with cancer. PROCEDURE: A HBHC program was carried out with 51 children (0-18 years) with cancer to assess its feasibility in terms of satisfaction, care preferences, safety, and cost. A controlled trial was conducted to assess children's health-related quality of life (HRQOL) using the parent-reported and self-reported PedsQL generic core scale and PedsQL cancer module, and the psychosocial impact on the family by PedsQL family impact module comprising a subsample of 28 children and 43 parents in the home care group, and 47 children and 66 parents receiving standard hospital care. RESULTS: All parents in the HBHC program were satisfied and preferred home care. There were no serious adverse events associated with HBHC, and costs did not increase. When adjusting for age, gender, diagnosis and time since diagnosis, we found significant higher HRQOL scores in parent-reported physical health (P = 0.04; 95% confidence interval (CI): -0.2-19.5) and worry (P = 0.04; 95% CI: -0.4-20.6) in the home-care group indicating better physical health and less worry for children in the home-care group. No significant difference was found in the Family Impact Module. CONCLUSION: This study indicates that HBHC is a feasible alternative to hospital care for children with cancer, and is greatly preferred by parents. Specific aspects of children's HRQOL may be improved with HBHC and the psychosocial burden on the family does not increase.

Supplementing the early diet of broilers with soy protein concentrate can improve intestinal development and enhance short-chain fatty acid-producing microbes and short-chain fatty acids, especially butyric acid.

BACKGROUND: Research on nutrition in early-life commonly focuses on the maturation of the intestine because the intestinal system is crucial for ensuring continued growth. To explore the importance of early nutrition regulation in animals, soy protein concentrate (SPC) was added to the early diet of broilers to investigate its effects on amino acid digestibility, intestinal development, especially intestinal microorganisms, and broiler metabolites. A total of 192 one-day-old Arbor Acres (AA) male broilers were randomly assigned to two experimental treatments with 8 replicates of 12 birds. The control group was fed a basal diet (control), and the treatment group was fed a basal diet supplemented with 12% SPC (SPC12) during the first 10 d (starter phase). From d 11 to 21 (grower phase) and d 22 to 42 (finisher phase), a basal diet was fed to both treatment groups. RESULTS: SPC reduced the pH value and acid-binding capacity of the starter diet (P < 0.05, d 10); SPC in the early diet enhanced the gizzard weight (P < 0.05, d 10 and d 42) and the ileum weight (P < 0.05, d 10) and decreased the weight and length of the jejunum (P < 0.05, d 10) and the relative length of the duodenum and jejunum (P < 0.05, d 10). At the same time, SPC enhanced villus height (P < 0.05, d 10) and muscle thickness in the jejunum and ileum (P < 0.05, d 10) and increased the number of goblet cells in the duodenum (P < 0.05, d 10). Meanwhile, SPC increased the Chao1 index and the ACE index (P < 0.05, d 10) and altered the composition of caecal microflora at d 10. SPC also increased the relative abundance of Alistipes, Anaerotruncus, Erysipelatoclostridium, Intestinimonas and Flavonifractor bacteria (P < 0.05, d 10). At the same time, the concentrations of caecal butyric acid and total short-chain fatty acids (SCFAs) were also increased in the SPC12 group (P < 0.05, d 10). CONCLUSIONS: In summary, the results showed that supplementing the starter diet of broilers with SPC has a significant effect on the early development of the intestine and the microflora.

Chronic Stress Induces Hippocampal Mitochondrial Damage in APPPS1 Model Mice and Wildtype Littermates.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. Despite decades of investigation, the etiology of AD is not fully understood, although emerging evidence suggest that chronic environmental and psychological stress plays a role in the mechanisms and contributes to the risk of developing AD. Thus, dissecting the impact of stress on the brain could improve our understanding of the pathological mechanisms. OBJECTIVE: We aimed to study the effect of chronic stress on the hippocampal proteome in male APPPS1 transgenic mice and wildtype (WT) littermates. METHODS: APPPS1 and WT mice were subjected to 4 weeks of chronic stress followed by 3 weeks of continued diurnal disruption. Hippocampal tissue was used for proteomics analysis using label-free quantitative DIA based LC-MS/MS analysis. RESULTS: We identified significantly up- and downregulated proteins in both APPPS1 and WT mice exposed to chronic stress compared to the control groups. Via interaction network mapping, significant proteins could be annotated to specific pathways of mitochondrial function (oxidative phosphorylation and TCA cycle), metabolic pathways, AD pathway and synaptic functions (long term potentiation). In WT mice, chronic stress showed the highest impact on complex I of the oxidative phosphorylation pathway, while in APPPS1 mice this pathway was compromised broadly by chronic stress. CONCLUSION: Our data shows that chronic stress and amyloidosis additively contribute to mitochondrial damage in hippocampus. Although these results do not explain all effects of chronic stress in AD, they add to the scientific knowledge on the topic.

Effects of Soy Protein Concentrate in Starter Phase Diet on Growth Performance, Blood Biochemical Indices, Carcass Traits, Immune Organ Indices and Meat Quality of Broilers.

Soybean meal (SBM) is high in antinutritional factors (ANFs), which is not conducive to the starter growth of broilers. The purpose of this study was to investigate the effects of soy protein concentrate (SPC) in starter diet on growth performance, carcass traits, meat quality, immune organ indices and blood biochemical indices of broilers. A total of 384 1-day-old Arbor Acres (AA) male broilers (46.05 ± 0.37 g) with similar body weight were randomly divided into 4 groups with 8 replicates in each group and 12 broilers in each replicate. The experiment was divided into three phases: in starter phase (1-10 d), birds were fed a corn-SBM-based basal mash diet (control) and the basal diet was supplemented with SPC at 4% (SPC4), 8% (SPC8), 12% (SPC12). In the grower phase (11-21 d) and the finisher phase (22-42 d), the birds in all four treatment groups were fed the same diets. The results showed that the body weight was significantly increased in the SPC8 and SPC12 groups of broilers at 10 d and 42 d (p < 0.05). The average daily gain was significantly increased in the SPC12 group of broilers at 1-10 d and 1-42 d (p < 0.05). The average daily feed intake was significantly increased in the SPC8 and SPC12 groups of broilers at 1-10 d (p < 0.05). The feed conversion rates at 1-42 d (p = 0.055) tended to decline in the SPC12 group. The carcass yield and the thymus indices were significantly increased in the SPC12 group of broilers at 42 d (p < 0.05). Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) tended to decline in SPC12 group at 10 d (p = 0.055) and total protein (TP) tended to increase in the SPC12 group at 42 d (p = 0.080). The contents of total cholesterol (T-CHO) and high-density lipoprotein (HDL) were significantly elevated in the SPC12 group of broilers at 42 d (p < 0.05). In conclusion, dietary inclusion of 12% SPC as a starter diet can be recommended due to the positive effects on broilers.

Impact of feeding modified soy protein concentrate in the starter phase on growth performance and gastrointestinal responses in broiler chickens through to day 42 of age.

Growth performance and physiological responses of feeding modified soy protein concentrate (MSPC, 72% CP) in the starter phase were investigated. A total of 1,216 d old male Ross x Ross 708 broiler chicks were placed in 32 floor pens based on BW, fed one of 4 (n = 8) corn-soybean meal-based diets formulated with 0, 7.7, 10.0 or 12.5% MSPC for 10 d and transitioned to common diets to d 42. Feed intake, BW, and mortality were measured. Samples of birds were bled on d 10 for plasma uric acid (PUA) and subsequently necropsied for organs weight and samples of pancreatic tissues for enzyme activity, jejunal tissues for enzyme activity and histomorphology and ceca digesta for microbial activity. Litter moisture was determined on d 36 and 42 and sample of birds were necropsied on d 42 for breast yield and ceca digesta sample for microbial activity. Feeding MSPC linearly (P < 0.001) increased starter growth performance. Overall (d 0-42), MSPC linearly (P = 0.05)improved FCR; The FCR was 1.566, 1.535, 1.488 and 1.527 for 0.0, 7.7, 10.0, and 12.5% MSPC, respectively. Feeding MSPC linearly (P ≤ 0.04) increased breast yield and decreased small intestine length, gizzard digesta pH, and PUA. Breast yield was 230, 238, 246, and 252 g/kg BW for 0.0, 7.7, 10.0, and 12.5% MSPC, respectively. Pancreatic and jejunal chymotrypsin and trypsin activities and histomorphology were not (P > 0.10) influenced by the diets. On d 10, MSPC linearly (P < 0.05) reduced ceca digesta abundance of Ruminococcaceae, E. Coli, and Clostridium but increased abundance of Bifidobacterium and the ratio of Lactobacilli and E. Coli. Birds fed MSPC showed linear (P = 0.01) increase in abundance of Bifidobacterium on d 42. Feeding MSPC linearly increased ceca digesta acetic (P = 0.01) and reduced propionic (P = 0.048), and iso butyric (P = 0.003) in 10 d old broiler chicken. In conclusion, up to 12.5% MSPC inclusion in the starter phase increased growth performance through to d 42 linked to enhanced gut health through reduction of enteric pathogens.

Impact of climate change effects on contamination of cereal grains with deoxynivalenol.

Climate change is expected to aggravate feed and food safety problems of crops; however, quantitative estimates are scarce. This study aimed to estimate impacts of climate change effects on deoxynivalenol contamination of wheat and maize grown in the Netherlands by 2040. Quantitative modelling was applied, considering both direct effects of changing climate on toxin contamination and indirect effects via shifts in crop phenology. Climate change projections for the IPCC A1B emission scenario were used for the scenario period 2031-2050 relative to the baseline period of 1975-1994. Climatic data from two different global and regional climate model combinations were used. A weather generator was applied for downscaling climate data to local conditions. Crop phenology models and prediction models for DON contamination used, each for winter wheat and grain maize. Results showed that flowering and full maturity of both wheat and maize will advance with future climate. Flowering advanced on average 5 and 11 days for wheat, and 7 and 14 days for maize (two climate model combinations). Full maturity was on average 10 and 17 days earlier for wheat, and 19 and 36 days earlier for maize. On the country level, contamination of wheat with deoxynivalenol decreased slightly, but not significantly. Variability between regions was large, and individual regions showed a significant increase in deoxynivalenol concentrations. For maize, an overall decrease in deoxynivalenol contamination was projected, which was significant for one climate model combination, but not significant for the other one. In general, results disagree with previous reported expectations of increased feed and food safety hazards under climate change. This study illustrated the relevance of using quantitative models to estimate the impacts of climate change effects on food safety, and of considering both direct and indirect effects when assessing climate change impacts on crops and related food safety hazards.

Myocellular triacylglycerol breakdown in females but not in males during exercise.

The resting content and use of myocellular triacylglycerol (MCTG) during 90 min of submaximal exercise [60% of peak oxygen uptake (VO(2 peak))] were studied in 21 eumenorrheic female and 21 male subjects at different training levels [untrained (UT), moderately trained (MT), and endurance trained (END)]. Males and females were matched according to their VO(2 peak) expressed relative to lean body mass, physical activity level, and training history. All subjects ingested the same controlled diet for 8 days, and all females were tested in the midfollicular phase of the menstrual cycle. Resting MCTG, measured with the muscle biopsy technique, averaged 48.4 +/- 4.2, 48.5 +/- 8.4, and 52.2 +/- 5.8 mmol/kg dry wt in UT, MT, and END females, respectively, and 34.1 +/- 4.9, 31.6 +/- 3.3, and 38.4 +/- 3.0 mmol/kg dry wt in UT, MT, and END males, respectively (P < 0.001, females vs. males in all groups). Exercise decreased MCTG content in the female subjects by an average of 25%, regardless of training status, whereas in the male groups MCTG content was unaffected by exercise. The arterial plasma insulin concentration was higher (P < 0.05) and the arterial plasma epinephrine concentration was lower (P < 0.05) in the females than in the males at rest and during exercise. MCTG use was correlated to the resting concentration of MCTG (P < 0.001). We conclude that resting content and use of MCTG during exercise are related to gender and furthermore are independent of training status.

Gender differences in substrate utilization during submaximal exercise in endurance-trained subjects.

Substrate utilization across the leg during 90 min of bicycle exercise at 58% of peak oxygen uptake (VO(2 peak)) was studied in seven endurance-trained males and seven endurance-trained, eumenorrheic females by applying arteriovenous catheterization, stable isotopes, and muscle biopsies. The female and male groups were matched according to VO(2 peak) per kilogram of lean body mass, physical activity level, and training history of the subjects. All subjects consumed the same diet, well controlled in terms of nutrient composition as well as energy content, for 8 days preceding the experiment, and all females were tested in the midfollicular phase of the menstrual cycle. During exercise, respiratory exchange ratio (RER) and leg respiratory quotient (RQ) were similar in females and males. Myocellular triacylglycerol (TG) degradation was negligible in males but amounted to 12.4 +/- 3.2 mmol/kg dry wt in females and corresponded to 25.0 +/- 6.0 and 5.0 +/- 7.3% of total oxygen uptake in females and males, respectively (P < 0.05). Utilization of plasma fatty acids (12.0 +/- 2.5 and 9.6 +/- 1.5%), blood glucose (13.6 +/- 1.5 and 14.3 +/- 1.5%), and glycogen (48.5 +/- 4.9 and 42.8 +/- 2.1%) were similar in females and males. Thus, in females, measured substrate oxidation accounted for 99% of the leg oxygen uptake, whereas in males 28% of leg oxygen uptake was unaccounted for in terms of measured oxidized lipid substrates. These findings may indicate that males utilized additional lipid sources, presumably very low density lipoprotein-TG or TG located between muscle fibers. On the basis of RER and leg RQ, it is concluded that no gender difference existed in the relative contribution from carbohydrate and lipids to the oxidative metabolism across the leg during submaximal exercise at the same relative workload. However, an effect of gender appears to occur in the utilization of the different lipid sources.