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The gut is composed of a single layer of intestinal epithelial cells and plays important roles in the digestion and absorption of nutrients, immune and barrier functions and amino acid metabolism. Weaning stress impairs piglet intestinal epithelium structural and functional integrities, which results in reduced feed intake, growth rates and increased morbidity and mortality. Several measures are needed to maintain swine gut development and growth performance after weaning stress. A large body of evidence indicates that, in weaning piglets, glutamine, a functional amino acid, may improve growth performance and intestinal morphology, reduce oxidative damage, stimulate enterocyte proliferation, modulate cell survival and death and enhance intestinal paracellular permeability. This review focuses on the effects of glutamine on intestinal health in piglets. The aim is to provide evidentiary support for using glutamine as a feed additive to alleviate weaning stress.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
A new generation of high power laser facilities will provide laser pulses with extremely high powers of 10 petawatt (PW) and even 100 PW, capable of reaching intensities of
in the laser focus. These ultra-high intensities are nevertheless lower than the Schwinger intensity
at which the theory of quantum electrodynamics (QED) predicts that a large part of the energy of the laser photons will be transformed to hard Gamma-ray photons and even to matter, via electron–positron pair production. To enable the investigation of this physics at the intensities achievable with the next generation of high power laser facilities, an approach involving the interaction of two colliding PW laser pulses is being adopted. Theoretical simulations predict strong QED effects with colliding laser pulses of
focused to intensities
Feeding ruminants a high-grain (HG) diet is a widely used strategy to improve milk yield and cost efficiency. However, it may cause certain metabolic disorders. At present, information about the effects of HG diets on the systemic metabolic profile of goats and the correlation of such diets with rumen bacteria is limited. In the present study, goats were randomly divided into two groups: one was fed the hay diet (hay; n = 5), while the other was fed HG diets (HG; n = 5). On day 50, samples of rumen contents, peripheral blood serum and liver tissues were collected to determine the metabolic profiles in the rumen fluid, liver and serum and the microbial composition in rumen. The results revealed that HG diets reduced (P < 0.05) the community richness and diversity of rumen microbiota, with an increase in the Chao 1 and Shannon index and a decrease in the Simpson index. HG diets also altered the composition of rumen microbiota, with 30 genera affected (P < 0.05). Data on the metabolome showed that the metabolites in the rumen fluid, liver and serum were affected (variable importance projection > 1, P <0.05) by dietary treatment, with 47, 10 and 27 metabolites identified as differentially metabolites. Pathway analysis showed that the common metabolites in the shared key pathway (aminoacyl-transfer RNA biosynthesis) in the rumen fluid, liver and serum were glycine, lysine and valine. These findings suggested that HG diets changed the composition of the rumen microbiota and metabolites in the rumen fluid, liver and serum, mainly involved in amino acid metabolism. Our findings provide new insights into the understanding of diet-related systemic metabolism and the effects of HG diets on the overall health of goats.
With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’s t-test and Mann–Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.
Recent results in the development of diode-driven high energy, high repetition rate, picosecond lasers, including the demonstration of a cryogenic Yb:YAG active mirror amplifier that produces 1.5 J pulses at 500 Hz repetition rate (0.75 kW average power) are reviewed. These pulses are compressed resulting in the generation of
duration, 1 J pulses with 0.5 kW average power. A full characterization of this high power cryogenic amplifier, including at-wavelength interferometry of the active region under
average power pump conditions, is presented. An initial demonstration of operation at 1 kW average power (1 J, 1 kHz) is reported.
Understanding the structural evolution of electrode material during electrochemical activity is important to elucidate the mechanism of (de)lithiation, and improve the electrochemical function based on the material properties. In this study, lithium vanadium oxide (LVO, LiV3O8) was investigated using ex-situ, in-situ, and operando experiments. Via a combination of in-situ X-ray diffraction (XRD) and density functional theory results, a reversible structural evolution during lithiation was revealed: from Li poor α phase (LiV3O8) to Li rich α phase (Li2.5V3O8) and finally β phase (Li4V3O8). In-situ and operando energy dispersive X-ray diffraction (EDXRD) provided tomographic information to visualize the spatial location of the phase evolution within the LVO electrode while inside a sealed lithium ion battery.
New immunotherapies have had great successes, but also incredibly debilitating side effects for patients. This discrepancy needs to be a focus of pharmaceutical companies because it will affect the way Health Technology Assessment (HTA) agencies review drugs. Two or three case studies of patient and caregiver experiences surrounding immuno-oncology clinical trials, both past and ongoing, will be used in order to gain a better understanding of how these trials have impacted individuals.
Conduct in-person or telephone interviews with patients and their caregivers to find out more about patient experiences and see how key takeaways can help pharmaceutical companies better prepare submissions for HTA agencies as they launch future immuno-oncology drugs.
Preliminary results indicated that a patient completed a course of treatment and is very happy with the results. She had metastatic melanoma on her scalp. When she was being prepared for surgery, two new tumors on her scalp were discovered. As a result, she was included in a melanoma clinical trial.
Another patient is still undergoing treatment and is responding, but is experiencing severe side effects that are impacting his life and that of his primary caregiver. He was hospitalized once for sepsis.
Patient experiences can wildly vary. It is an area that needs more careful study, using both formal metrics and individual stories. Giving more attention to quality of life creates an opportunity for stronger submissions to HTA agencies and better assessments by those agencies.
Immunotherapies are a relatively new innovative class of drug that have garnered excitement in the fight against cancer. In 2011, the immunotherapy drug, ipilimumab, was approved. Since then, four additional drugs have gained approval. This analysis evaluates the initial reception of immunotherapies by Health Technology Assessment (HTA) agencies.
The Context Matters Data Model was used to evaluate the regulatory and HTA agency decisions surrounding the five approved immunotherapies through November 2016: atezolizumab, elotuzumab, ipilimumab, nivolumab, and pembrolizumab. Thirty-three labels from Australia, Canada, Europe, and the United States, and ninety-two assessments from Agenzia Italiana del Farmaco (AIFA), Gemeinsamer Bundesausschuss (Federal Joint Committee; G-BA), Haute Autorité de Santé (French National Authority for Health; HAS), Institute for Clinical and Economic Review (ICER), Institute for Quality and Efficiency in Health Care (IQWiG), National Institute for Health and Care Excellence (NICE), Pharmaceutical Benefits Advisory Committee (PBAC), pan-Canadian Oncology Drug Review (pCODR), and Scottish Medicines Consortium (SMC) were found. Using a sample t-test and a chi-squared test, reimbursement agencies’ decisions were evaluated, and the clinical and economic factors that went into these decisions were examined.
Of the evaluated reviews: sixty-four were for melanoma indications, fourteen were for non-small-cell lung cancer (NSCLC) indications, and seven were for kidney cancer indications. Many of the reviews did not reach any decision, but 75 percent of HTA decisions (n = 72; p = .0000) reached were positive. Elotuzumab, approved for multiple myeloma, received a positive decision from G-BA and a negative one from SMC. There was an association between different disease conditions or drugs and the rate of positive decisions.
For reviews that had clinical reasons for their decisions, 72.9 percent (n = 59; p = .0000) had positive clinical rationales that were associated with positive decisions (p = .000). Economic rationales for decisions were more mixed, with only 48.4 percent (n = 31; p = .0000) receiving positive decisions. Positive economic evaluations were also associated with positive decisions (p = .000). Atezolizumab, approved only in the United States at the time of this writing, has yet to be reviewed by any of the HTA agencies.
Immunotherapies are promising new options for the treatment of cancer. Thus far, reception by HTA agencies has generally been positive.
An experiment was carried out to evaluate the short-term effect of supplementing a nucleotide-rich yeast extract (NRYE) on growth performance, gut structure, immunity and microflora of piglets raised under sanitary and unsanitary conditions. A total of 84, 21-day old piglets were used in this study; 42 piglets were raised in a room designated as the clean room that was washed once per week, whereas the other 42 piglets were raised in a room designated as the unclean room in which 7 kg of manure from the sow herd was spread on each pen floor on day 1 and 7 and the room was not washed throughout the experiment. The pigs were fed a corn–soybean meal-based diet without or with 0.1% NRYE. Each treatment had 7 replicate pens in each room, and each pen housed 3 pigs. Feed disappearance and BW were recorded on day 1 and 14. On day 14, one pig per pen was euthanized to collect ileum, mesenteric lymph nodes and spleen tissues, and cecum and colon digesta. Overall, NRYE supplementation did not affect growth performance in both clean and unclean conditions, improved kidney weight in both clean (P=0.0002) and unclean room (P<0.0001) and tended to improve the villus height/crypt depth ratio in the clean room (P=0.073). Supplementing NRYE was associated with upregulation of Ileal programmed cell death gene-1 (P=0.0003), interleukin (IL)-1β (P<0.0001), IL-6 (P=0.0003), IL-10 (P<0.0001) and tumor necrosis factor-α (TNF-α) (P<0.0001) in pigs raised in the unclean room. Supplementing the NRYE in pigs raised in the clean room suppressed growth of cecal Enterobacteriacea (P<0.0001) members and colonic Enterococcus spp. (P<0.019), improved proliferation of cecal Lactobacillus spp. (P<0.002) and colonic Clostridium cluster IV (P<0.011) and XVIa members (P<0.0002). Supplementing the NRYE in the unclean room improved proliferation of cecal Clostridium cluster IV (P<0.026) and suppressed proliferation of colonic Enterococcus spp. (P<0.037). In conclusion, supplementing the NRYE to piglets under unsanitary conditions improved ileal immune response by upregulating inflammatory cytokines, and positively modulated proliferation of beneficial gut bacteria and suppression of harmful ones in both clean and unclean rooms.
Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into ‘success’ and ‘failure’ groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (<18·5), long duration of previous treatment (>6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.
The law of unilateral acts and the law of treaties are generally considered to be two distinct areas of international law. While the former governs the effect of unilateral undertakings by States, the latter governs, inter alia, the formation, interpretation, termination, and suspension of treaties. In 2011, the International Law Commission (ILC) concluded a two-decade study on reservations. One of its most remarkable insights is the argument that reservations ought to be considered ‘unilateral acts’. Thus, certain rules pertaining the law of unilateral acts ought to apply to reservations. This article critically examines the ILC's novel proposal as well as its attempt to provide answers to contemporary questions on reservations through conceptualizing reservations as unilateral acts.
Experiments on the National Ignition Facility show that multi-dimensional effects currently dominate the implosion performance. Low mode implosion symmetry and hydrodynamic instabilities seeded by capsule mounting features appear to be two key limiting factors for implosion performance. One reason these factors have a large impact on the performance of inertial confinement fusion implosions is the high convergence required to achieve high fusion gains. To tackle these problems, a predictable implosion platform is needed meaning experiments must trade-off high gain for performance. LANL has adopted three main approaches to develop a one-dimensional (1D) implosion platform where 1D means measured yield over the 1D clean calculation. A high adiabat, low convergence platform is being developed using beryllium capsules enabling larger case-to-capsule ratios to improve symmetry. The second approach is liquid fuel layers using wetted foam targets. With liquid fuel layers, the implosion convergence can be controlled via the initial vapor pressure set by the target fielding temperature. The last method is double shell targets. For double shells, the smaller inner shell houses the DT fuel and the convergence of this cavity is relatively small compared to hot spot ignition. However, double shell targets have a different set of trade-off versus advantages. Details for each of these approaches are described.
Far-infrared (FIR), ultraviolet (UV), and soft X-ray observations are easily degraded by dust and gas between the source and the telescope. They must be made from space, where they are still affected by the interstellar medium (ISM) of our Galaxy. Fortunately the ISM is quite patchy, with several “cosmic windows” covering ∼ 100 deg2 of sky having exceptionally low interstellar extinction and cirrus emission. Since the universe is nearly isotropic, these windows contain representative samples of cosmologically distant sources and will be the targets of deep multiwavelength studies including SWIRE, GALEX/DIS, and XMM-LSS. Overlapping optical and radio surveys provide essential source identifications, redshifts, morphologies, and continuum spectra. The prototype VLA survey (see http://www.cv.nrao.edu/sirtf_fls/) covers the 5 deg2 SIRTF First-Look Survey (FLS) and is being used to identify the expected FIR sources in advance. Most will be star-forming galaxies obeying the very tight far-infrared/radio correlation and thus continuum radio sources stronger than S ≈ 100 μJy at 1.4 GHz. Proposed VLA surveys covering the remaining “cosmic windows” will be useful for studying the evolution of obscured AGNs, clusters, and other uncommon objects.
This paper presents an analytical approach to analyze the vertical vibration of a simply supported beam subjected to pedestrian-induced loads. The loading time history of an individual footstep is simplified as a rectangular force pulse, and each identical footstep load acts at different locations along the beam depending on a step length. Although the loading model is very simple, it enables us to find analytical relations between the pacing parameters and the beam response. The results showed that the dependence of the pacing period, footstep contact duration, time delay of traveling between two pedestrians on the natural period of the beam as well as the step length can influence the dynamic response of the beam significantly.
Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia.
A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).
Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB.
IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.
Ectropis grisescens Warren and Ectropis obliqua (Prout) are two morphologically similar sibling species with overlapping ranges. In this study, manipulative laboratory experiments were conducted to examine the possibility of reproductive interference in sympatric populations of E. grisescens and E. obliqua and the potential consequences of the mating interaction. Our results showed that the presence of males or females of different species could incur mating interference and significant reduction of F1 offspring. The reduction was not significant relevant to the initial relative abundance of E. grisescens and E. obliqua. Detailed observations of mating opportunity showed that female mating frequencies of both species were not significantly affected by the absolute species density, but the mating success of E. obliqua females with conspecific males depended on species ratio. In addition, adding males to the other species resulted in lower number of offspring suggesting that the males’ behaviour might be linked with mating interference. Males of both E. grisescens and E. obliqua could interfere the intraspecific mating of the other species, but the impact of the mating interference differed. These combined data indicated that asymmetric reproductive interference existed in E. grisescens and E. obliqua under laboratory conditions, and the offspring of the mixed species were significantly reduced. The long term outcome of this effect is yet to be determined since additional reproductive factors such as oviposition rate and progeny survival to adulthood may reduce the probability of demographic displacement of one species by the other in overlapping niches.