Some cost problems in the Hawaiian sugar industry

It is not the intention of this article to present a complete cost system, nor to give a detailed description of the various cost accounts which are used in the Hawaiian sugar industry, but rather to outline some of the many and varied problems of the industry which exercise a direct influence upon the cost accounting procedure. It will be found, for example, that the human factor has a much more important influence on costs and cost procedure than is generally the case in other industries, because the laborer and his family are practically wards of the employer, and their care is one of his chief problems and one of the important items in his costs

Scaling behaviour of the critical current in clean epitaxial Ba(Fe1-xCox)2As2 thin films

The angular-dependent critical current density, Jc(theta), and the upper critical field, Hc2(theta), of epitaxial Ba(Fe1-xCox)2As2 thin films have been investigated. No Jc(theta) peaks for H || c were observed regardless of temperatures and magnetic fields. In contrast, Jc(theta) showed a broad maximum at theta=90 degree, which arises from intrinsic pinning. All data except at theta=90 degree can be scaled by the Blatter plot. Hc2(theta) near Tc follows the anisotropic Ginzburg-Landau expression. The mass anisotropy increased from 1.5 to 2 with increasing temperature, which is an evidence for multi-band superconductivity.Comment: Accepted in Physical Review B rapid communication

Proteomic changes in serum of first onset, antidepressant drug-naïve major depression patients

Major depressive disorder (MDD) is a complex and multi-factorial disorder. Although genetic factors and other molecular aspects of MDD have been widely studied, the underlying pathological mechanisms are still mostly unknown. We sought to investigate the pathophysiology of MDD by identifying and characterising serum molecular differences and their correlation to symptom severity in first onset, antidepressant drug-naïve MDD patients. We performed an exploratory molecular profiling study on serum samples of MDD patients and controls using multiplex immunoassay and label-free liquid chromatography mass spectrometry in data independent mode (LC-MSE). We included two independent cohorts of first onset, antidepressant drug-naïve MDD patients (n = 23 and 15) and matched controls (n = 42 and 21) in our study in order to validate the results. The main outcome included the following list of circulatory molecules changing and/or correlating to symptom severity: angiotensin-converting enzyme, acute phase proteins (e.g. ferritin and serotransferrin), brain-derived neurotrophic factor, complement component C4-B, cortisol, cytokines (e.g. macrophage migration inhibitory factor and interleukin-16), extracellular newly identified receptor for advanced glycosylation end products-binding protein, growth hormone and superoxide dismutase-1. This study provides evidence of an increased pro-inflammatory and oxidative stress response, followed by a hyperactivation of the HPA-axis in the acute stages of first onset MDD, as well as a dysregulation in growth factor pathways. These findings help to elucidate MDD related pathways in more detail and further studies may lead to identification of novel drug targets, inc

Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum

Recent evidence suggests that comorbidities between neuropsychiatric conditions and metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medication, such as a higher risk of type 2 diabetes and cardiovascular disease, which result in increased mortality. In the present study we compare the expression of key metabolic proteins, including the insulin receptor (CD220), glucose transporter 1 (GLUT1) and fatty acid translocase (CD36), on peripheral blood mononuclear cell subtypes from patients across the neuropsychiatric spectrum, including schizophrenia, bipolar disorder, major depression and autism spectrum conditions (n = 25/condition), relative to typical controls (n = 100). This revealed alterations in the expression of these proteins that were specific to schizophrenia. Further characterization of metabolic alterations in an extended cohort of first-onset antipsychotic drug-naïve schizophrenia patients (n = 58) and controls (n = 63) revealed that the relationship between insulin receptor expression in monocytes and physiological insulin sensitivity was disrupted in schizophrenia and that altered expression of the insulin receptor was associated with whole genome polygenic risk scores for schizophrenia. Finally, longitudinal follow-up of the schizophrenia patients over the course of antipsychotic drug treatment revealed that peripheral metabolic markers predicted changes in psychopathology and the principal side effect of weight gain at clinically relevant time points. These findings suggest that peripheral blood cells can provide an accessible surrogate model for metabolic alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic complications following antipsychotic therapy.This work was supported by grants from the Stanley Medical Research Institute (SMRI); the Engineering and Physical Sciences Research Council UK (EPSRC); the Dutch Government-funded Virgo consortium (ref. FES0908); the Netherlands Genomics Initiative (ref. 050-060-452); the European Union FP7 funding scheme: Marie Curie Actions Industry Academia Partnerships and Pathways (ref. 286334, PSYCH-AID project); SAF2016-76046-R and SAF2013-46292-R (MINECO) and PI16/00156 (isciii and FEDER)

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)

Genetic modifiers in rare disorders: the case of fragile X syndrome.

Methods employed in genome-wide association studies are not feasible ways to explore genotype-phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations

Towards a blood-based diagnostic panel for bipolar disorder

BACKGROUND: Bipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD. METHODS AND FINDINGS: We performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies. We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC)?0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel. CONCLUSIONS: An early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.We would like to thank all participants of this study as well as all participating centres for the collaboration and for access to the serum samples. We gratefully acknowledge support by the Stanley Medical Research Institute (no. 07R-1888). The infrastructure for the NESDA study (www.nesda.nl) has been funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and participating universities (VU University Medical Center, Leiden University Medical Center, University Medical Center Groningen). DNC, DWN and NSW efforts were funded by the Stanley Medical Research Institute and the US Department of the Army