An Investigation of Offset Printability in Folding Boxboard Using a Letterpress Printing Test

The primary reason for this investigation was to determine if a simple letterpress test could be used to predict the print quality of folding boxboard printed by the offset method. The experimental plan was to compare the objective ranking of print quality in the laboratory prints with the subjective ranking of print quality in the commercial prints. If the rankings correlated favorably, there would be reason to suspect that this type of test might be applicable in predicting the millroom print quality of folding boxboard. It was found that the hoped-for correlation did not exist in this particular case primarily because of sampling procedures. However, it appears that an objective range in print quality can be determined using these methods in the laboratory. An idea for further work in this specific area is offered in the conclusion of this paper

Assessment of a newly designed double-barreled bullet-shooting stunner for adequate stunning of water buffaloes

To ensure animal welfare at slaughter, rapid stunning is required to render the animal deeply unconscious. In cattle, captive-bolt stunners are typically used for this purpose. However, with regard to their impact force and maximum length of approximately 120 mm, such captive-bolt stunners are not suitable for stunning water buffaloes due to anatomical characteristics of the skull. In water buffaloes the bone layer is thicker and the distance from the point of attachment of the captive-bolt stunner to the relevant brain region is longer. For this reason, a special bullet-shooting stunner was developed, which is similar in size and handling to a standard captive-bolt stunner, but instead of a bolt, it fires a bullet. Actually, even two bullets can be loaded so that a follow-up shot can be fired immediately if necessary. In this study, the bullet-shooting stunner was tested using two different types of hunting ammunition for stunning water buffaloes during regular slaughter

BigBovid- Evaluation of a Newly Developed 9 mm Bullet-Shooting Stunner for Adequate Stunning of Heavy Cattle

The stunning of heavy cattle and water buffalo is an animal welfare problem, as conventional cartridge fired captive-bolt stunners are not suitable due to the thicker skull bones and the greater depth of penetration required to reach and damage the relevant brain regions for deep unconsciousness. This current animal welfare problem requires a suitable and feasible as well as commercially available and legally approved stunning device to ensure deep unconsciousness of these animals. In this study, the use of a newly developed bullet-shooting stunner, the BigBovid, with two different types of hunting ammunition, namely .38 SPL FMJ-TC and .357 MAG FTX ® bullets, was evaluated on 22 heavy cattle (mean weight: 1062.27 kg, standard deviation: 124.09 kg). In ballistic experiments, the BigBovid reached a mean energy density of 8.18 J/mm2 (mean error: 0.45 J/mm2) for the .38 SPL FMJ-TC and 17.56 J/mm2 (mean error: 2.67 J/mm2) for the .357 MAG FTX ®. In in vivo experiments, the use of the .38 SPL FMJ-TC resulted in overpenetration three times. The .357 MAG FTX ® bullets showed to be more advantageous, because on the one hand no overpenetration occurred and on the other hand the bullets fragmented into small parts after penetration into the skull. The fragments were scattered in the brain tissue, such as the thalamus and the brain stem, and thus there is a high probability to damage the brain regions relevant for deep unconsciousness. Based on the results of this study, the use of the BigBovid in combination with the .357 MAG FTX ® bullet is found to be suitable for stunning heavy cattle. Keywords: animal welfare; concussion; desensitization; heavy bulls; slaughterin

Long-term renal safety profile of ibandronate 6 mg infused over 15 minutes

In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3-4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate

A common polymorphism in SNCA is associated with accelerated motor decline in GBA-Parkinson's disease.

A growing number of genetic susceptibility factors have been identified for Parkinson’s disease (PD). The combination of inherited risk variants is likely to affect not only risk of developing PD but also its clinical course. Variants in the GBA gene are particularly common, being found in approximately 5 to 10% of patients, and they lead to more rapid disease progression1. However, the effect of concomitant genetic risk factors on disease course in GBA-PD is not known.The CamPaIGN study has received financial support from the Wellcome Trust, the Medical Research Council, Parkinson’s UK and the Patrick Berthoud Trust. CHWG is supported by an RCUK/UKRI Innovation Fellowship awarded by the Medical Research Council. RAB is supported by the Wellcome Trust Stem Cell Institute (Cambridge). TBS received financial support from the Cure Parkinson’s Trust. The study is also supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre Dementia and Neurodegeneration Theme (reference number 146281). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. CRS' work is supported in part by NIH grants R01AG057331, U01NS100603, R01AG057331, and the American Parkinson Disease Association. Illumina MEGA Chip genotyping was made possible by a philanthropic investment from Dooley LLC (to Brigham & Women's Hospital and CRS)

12．グルタミン酸ナトリウムはglucagon like peptide-1の食後早期の分泌を促進し, 食後血糖の上昇を抑制する

The purpose of this study was to compare the growth and nutritional status of infants fed different diets, some of whom received a low-fat formula. Beginning at four to six months of age, 101 infants were fed whole cow\u27s milk, one of two low-fat follow-up formulas, or a standard infant formula until 12 months of age. Weight, recumbent length, and head circumference were measured at one-month intervals. Analyses of status (values at an age) for all examinations showed no significant differences among the feeding groups in status for weight or recumbent length, but there were significant differences in head circumference for boys and for girls after adjustments for the initial values. Head circumferences were smaller in those fed whole cow\u27s milk and relatively large in those fed follow-up formula, but these differences were small and not of clinical significance. Comparisons with national reference data showed growth in weight, recumbent length, and head circumference was normal regardless of feeding group. These results indicate that, during the second half year of infancy, the use of lower fat concentrations in the follow-up formulas did not retard growth in weight, recumbent length, or head circumference

¹H NMR based metabolomics of CSF and blood serum: a metabolic profile for a transgenic rat model of Huntington disease

AbstractHuntington disease (HD) is a hereditary brain disease. Although the causative gene has been found, the exact mechanisms of the pathogenesis are still unknown. Recent investigations point to metabolic and energetic dysfunctions in HD neurons.Both univariate and multivariate analyses were used to compare proton nuclear magnetic resonance spectra of serum and cerebrospinal fluid (CSF) taken from presymptomatic HD transgenic rats and their wild-type littermates. N-acetylaspartate (NAA), was found to be significantly decreased in the serum of HD rats compared to wild-type littermates. Moreover, in the serum their levels of glutamine, succinic acid, glucose and lactate are significantly increased as well. An increased concentration of lactate and glucose is also found in CSF. There is a 1:1 stoichiometry coupling glucose utilization and glutamate cycling. The observed increase in the glutamine concentration, which indicates a shutdown in the neuronal-glial glutamate-glutamine cycling, results therefore in an increased glucose concentration. The elevated succinic acid concentration might be due to an inhibition of succinate dehydrogenase, an enzyme linked to the mitochondrial respiratory chain and TCA cycle. Moreover, reduced levels of NAA may reflect an impairment of mitochondrial energy production. In addition, the observed difference in lactate supports a deficiency of oxidative energy metabolism in rats transgenic for HD as well.The observed metabolic alterations seem to be more profound in serum than in CSF in presymptomatic rats. All findings suggest that even in presymptomatic rats, a defect in energy metabolism is already apparent. These results support the hypothesis of mitochondrial energy dysfunction in HD

Impact of GBA1 variants on long-term clinical progression and mortality in incident Parkinson’s disease

Funder: Foundation for the National Institutes of Health; FundRef: http://dx.doi.org/10.13039/100000009Funder: Van Geest FoundationFunder: Patrick Berthoud Charitable Trust; FundRef: http://dx.doi.org/10.13039/501100004218Funder: Cure Parkinson's TrustFunder: Michael J Fox FoundationFunder: Innovate UK; FundRef: http://dx.doi.org/10.13039/501100006041Funder: Dooley LLCFunder: American Parkinson's disease associationFunder: Medical Research Council; FundRef: http://dx.doi.org/10.13039/501100000265Funder: Cambridge Centre for Parkinson-PlusFunder: Parkinson's UK; FundRef: http://dx.doi.org/10.13039/501100000304Funder: John Black charitable foundationFunder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272Funder: Van Andel Research Institute; FundRef: http://dx.doi.org/10.13039/100006019Introduction: Variants in the GBA1 gene have been identified as a common risk factor for Parkinson’s disease (PD). In addition to pathogenic mutations (those associated with Gaucher disease), a number of ‘non-pathogenic’ variants also occur at increased frequency in PD. Previous studies have reported that pathogenic variants adversely affect the clinical course of PD. The role of ‘non-pathogenic’ GBA1 variants on PD course is less clear. In this study, we report the effect of GBA1 variants in incident PD patients with long-term follow-up. Methods: The study population consisted of patients in the Cambridgeshire Incidence of Parkinson’s disease from General Practice to Neurologist and Parkinsonism: Incidence, Cognition and Non-motor heterogeneity in Cambridgeshire cohorts. Patients were grouped into non-carriers, carriers of ‘non-pathogenic’ GBA1 variants and carriers of pathogenic GBA1 mutations. Survival analyses for time to development of dementia, postural instability and death were carried out. Cox regression analysis controlling for potential confounders were used to determine the impact of GBA1 variants on these outcome measures. Results: GBA1 variants were identified in 14.4% of patients. Pathogenic and ‘non-pathogenic’ GBA1 variants were associated with the accelerated development of dementia and a more aggressive motor course. Pathogenic GBA1 variants were associated with earlier mortality in comparison with non-carriers, independent of the development of dementia. Discussion: GBA1 variants, including those not associated with Gaucher disease, are common in PD and result in a more aggressive disease course

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

The price of tumor control

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects