Refined conditions for V-shaped optimal sequencing on a single machine to minimize total completion time under combined effects

We address single machine scheduling problems for which the actual processing times of jobs are subject to various effects, including a positional effect, a cumulative effect and their combination. We review the known results on the problems to minimize the makespan, the sum of the completion times and their combinations and identify the problems for which an optimal sequence cannot be found by simple priority rules such as SPT (Shortest Processing Time) and/or LPT (Longest Processing Time). Typically, these are problems to minimize the sum of the completion times under a deterioration effect, and we verify under which conditions for these problems an optimal permutation is V-shaped (an LPT subsequence followed by an SPT subsequence). We demonstrate that previously used techniques for proving that an optimal sequence is V- shaped are not properly justified. We use the corrected method to describe a wide range of problems with a pure positional effect and a combination of a cumulative effect with a positional effect for which an optimal sequence is V-shaped. On other hand, we show that even the refined approach has its limitations

Diagnostic model development for schizophrenia based on peripheral blood mononuclear cell subtype-specific expression of metabolic markers

A significant proportion of the personal and economic burden of schizophrenia can be attributed to the late diagnosis or misdiagnosis of the disorder. A novel, objective diagnostic approaches could facilitate the early detection and treatment of schizophrenia and improve patient outcomes. In the present study, we aimed to identify robust schizophrenia-specific blood biomarkers, with the goal of developing an accurate diagnostic model. The levels of selected serum and peripheral blood mononuclear cell (PBMC) markers relevant to metabolic and immune function were measured in healthy controls (n?=?26) and recent-onset schizophrenia patients (n?=?36) using multiplexed immunoassays and flow cytometry. Analysis of covariance revealed significant upregulation of insulin receptor (IR) and fatty acid translocase (CD36) levels in T helper cells (F?=?10.75, P?=?0.002, Q?=?0.024 and F?=?21.58, P?=?2.8?×?10?5, Q?=?0.0004, respectively), as well as downregulation of glucose transporter 1 (GLUT1) expression in monocytes (F?=?21.46, P?=?2.9?×?10?5, Q?=?0.0004). The most robust predictors, monocyte GLUT1 and T helper cell CD36, were used to develop a diagnostic model, which showed a leave-one-out cross-validated area under the receiver operating characteristic curve (AUC) of 0.78 (95% CI: 0.66?0.92). The diagnostic model was validated in two independent datasets. The model was able to distinguish first-onset, drug-naïve schizophrenia patients (n?=?34) from healthy controls (n?=?39) with an AUC of 0.75 (95% CI: 0.64?0.86), and also differentiated schizophrenia patients (n?=?22) from patients with other neuropsychiatric conditions, including bipolar disorder, major depressive disorder and autism spectrum disorder (n?=?68), with an AUC of 0.83 (95% CI: 0.75?0.92). These findings indicate that PBMC-derived biomarkers have the potential to support an accurate and objective differential diagnosis of schizophrenia.ACKNOWLEDGEMENTS: We are grateful to the participants and their families for their cooperation in this study. We would like to thank blood donors and the clinical centres, for the provision of biological samples, in addition, to supporting staff at the affiliated institutions. We also thank IDIVAL biobank (Inés Santiuste and Jana Arozamena) and UMCU Biobank for clinical sample and data preparation, as well as the PAFIP members for the data collection. This work was supported by the Stanley Medical Research Institute (grant number: 12T-008) and the Dutch Research Council (NWO; grant number: 40–00812–98–12154) received by IES; by grants to SB from the Stanley Medical Research Institute (SMRI) and the Engineering and Physical Sciences Research Council UK (EPSRC); and by grants to BC-F: SAF2016–76046-R and SAF2013–46292-R (MINECO) and PI16/00156 (ISCIII and FEDER)

Identification of Stage-Specific Breast Markers using Quantitative Proteomics

YesMatched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Cyprus Research Promotion Foundation, Yorkshire Cancer Researc

Exploring peripheral biomarkers of response to simvastatin supplementation in schizophrenia

Schizophrenia is one of the most debilitating mental disorders, and its diagnosis and treatment present significant challenges. Several clinical trials have previously evaluated the effectiveness of simvastatin, a lipid-lowering medication, as a novel add-on treatment for schizophrenia. However, treatment effects varied highly between patients and over time. In the present study, we aimed to identify biomarkers of response to simvastatin in recent-onset schizophrenia patients. To this end, we profiled relevant immune and metabolic markers in patient blood samples collected in a previous clinical trial (ClinicalTrials.gov: NCT01999309) before simvastatin add-on treatment was initiated. Analysed sample types included serum, plasma, resting-state peripheral blood mononuclear cells (PBMCs), as well as PBMC samples treated ex vivo with immune stimulants and simvastatin. Associations between the blood readouts and clinical endpoints were evaluated using multivariable linear regression. This revealed that changes in insulin receptor (IR) levels induced in B-cells by ex vivo simvastatin treatment inversely correlated with in vivo effects on cognition at the primary endpoint of 12 months, as measured using the Brief Assessment of Cognition in Schizophrenia scale total score (standardised β ± SE = −0.75 ± 0.16, P = 2.2 × 10−4, Q = 0.029; n = 21 patients). This correlation was not observed in the placebo group (β ± SE = 0.62 ± 0.39, P = 0.17, Q = 0.49; n = 14 patients). The candidate biomarker explained 53.4 % of the variation in cognitive outcomes after simvastatin supplementation. Despite the small sample size, these findings suggest a possible interaction between the insulin signalling pathway and cognitive effects during simvastatin therapy. They also point to opportunities for personalized schizophrenia treatment through patient stratification.</p

How effective is a powered toothbrush as compared to a manual toothbrush? A systematic review and meta‐analysis of single brushing exercises

Objectives: In adult participants, what is, following a single brushing exercise, the efficacy of a powered toothbrush (PTB) as compared to a manual toothbrush (MTB) on plaque removal?. Methods: MEDLINE-PubMed and Cochrane-CENTRAL were searched from inception to February 2019. The inclusion criteria were (randomized) controlled clinical trials conducted in human subjects ≥18 years of age, in good general health and without periodontitis, orthodontic treatment, implants and/or removable prosthesis. Papers evaluating a PTB compared with a MTB in a single brushing exercise were included. When plaque scores were assessed according to the Quigley-Hein plaque index (Q&HPI) or the Rustogi modified Navy plaque index (RMNPI). From the eligible studies, data were extracted. A meta-analysis and subanalysis for brands and mode of action being oscillating-rotating (OR) and side-to-side (SS) were performed when feasible. Results: Independent screening of 3450 unique papers resulted in 17 eligible publications presenting 36 comparisons. In total, 28 comparisons assessed toothbrushing efficacy according to the Q&HPI and eight comparisons used the RMNPI. Results showed a significant effect in favour of the PTB. The difference of Means (DiffM) was −0.14 (P < 0.001; 95%CI [−0.19; −0.09]) for the Q&HPI and −0.10 (P < 0.001; 95%CI [−0.14; −0.06]) for the RMNPI, respectively. The subanalysis on the OR mode of action showed a DiffM −0.16 (P < 0.001; 95%CI [−0.22, −0.10]) for the Q&HPI. For the SS mode of action using RMNPI, the DiffM showed −0.10 (P < 0.001; 95%CI [−0.15; −0.05]). The subanalysis for brands showed for the P&G OR PTB using the Q&HPI a DiffM of −0.15 (P < 0.001; 95%CI [−0.22; −0.08]) and the Colgate SS for RMNPI showed a DiffM of −0.15 (P < 0.001; 95%CI [−0.18; −0.12]). Conclusion: There is moderate certainty that the PTB was more effective than the MTB with respect to plaque removal following a single brushing exercise independent of the plaque index scale that was used