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Negative emission technologies(NETs) have now become necessary in global decarbonization strategies, particularly, in reaching net-zero emissions. The marginal abatement cost(MAC) curve that graphs decarbonization strategies according to increasing cost-effectiveness has been used in net-zero emissions planning using NETs. However, the net-zero emissions targeting and the calculation of the total system cost are done manually in the graphical approach, which is cumbersome and inaccurate. To address these limitations, this work presents two alternative approaches based on MAC curves in net-zero emissions planning. The first approach is net-zero emissions planning by algebraic targeting(NEPAT). NEPAT involves the use of a cascade table to determine the negative emissions deficit, which is then followed by technology capacity adjustments to reach net-zero emissions. Although NEPAT improves the laboriousness and inaccuracy issues of the graphical technique in calculating the total system cost, targeting and optimization are done repeatedly and manually. To further improve the algebraic approach, the automated marginal abatement cost(AMAC) model is proposed, where mathematical programming is used to automatically target net-zero emissions based on user-defined objective functions and constraints. Both approaches enable the automatic calculation of costs, which is a limitation of the traditional MAC curve. The two approaches are demonstrated in a system of CO2-emitting sources and NETs. NEPAT has the advantage of increased interactivity with the model, while the AMAC has the advantage of optimization and ease of use. Both techniques contribute to decarbonization planning to reach net-zero emissions.

Refrigeration cycles employed for process cooling in industrial settings are known to be very energy-intensive. With the rise in energy demand across the globe, it is imperative that these systems are monitored and optimised to improve thermal efficiency and minimise energy consumption. While process simulators have been widely employed for process monitoring of refrigeration systems for optimisation and “what-if” scenarios, it is generally not suitable for remote monitoring due to their high computational cost. This is where machine learning (ML) models stand out, as they can be executed up to several orders of magnitude quicker than their corresponding first principle simulation model. In this paper, a case study is presented for a two-stage refrigeration system that covers data management, hybrid modelling (combining process simulation and ML), optimisation and online deployment. This case study demonstrates the workflow for constructing a refrigeration system ML model and deploying it to an online monitoring and prediction dashboard. Five different ML algorithms, namely multivariate linear regression (MLR), regression trees (RTs), random forests (RFs), extreme gradient boosting (XGBoost) and artificial neural networks (ANNs) were tested and evaluated to determine the most suitable algorithm to represent the behaviour of the refrigeration system. The results have shown that the XGBoost algorithm outperformed the other four algorithms as demonstrated by the lowest mean absolute error (MAE) and root mean squared error (RMSE). A significant improvement in performance was achieved after the XGBoost model was optimised via hyperparameter tuning and displayed an 86.40% and 82.35% improvement in terms of the MAE and RMSE. The results obtained from this study serve as a good benchmark for future modelling of refrigeration systems with XGBoost.

Understanding compulsive drinking behavior is key to improving outcomes in the treatment of addiction. In the present study, we investigated compulsive‐like drinking in alcohol‐addicted rats using the alcohol deprivation effect (ADE) model of relapse behavior, which involves repeated deprivation and reintroduction phases; the latter approximate relapse. High‐resolution longitudinal drinking and locomotor data were measured while rats (n= 30) underwent a four‐bottle (water, 5%, 10%, 20% alcohol v/v) free‐choice ADE paradigm. Alcohol bottles were adulterated with the bitter compound quinine during a reintroduction phase to test for compulsive behavior. We characterized how drinking and locomotor behavior during ADE + quinine differed from a regular ADE and how, at the individual level, behavioral parameters extracted from the regular ADE related to compulsive‐like drinking. Associations of drinking with locomotor activity were also examined. In the ADE with quinine, we observed reduced consumption of alcohol and a shift to preference for stronger alcohol. Quinine acted by decreasing both the access size and frequency of drinking of 5% alcohol while increasing the frequency of consumption of 20% alcohol. Preference for higher alcohol concentrations prior to the quinine challenge was associated with greater compulsive‐like drinking behavior; higher baseline consumption of 20% alcohol correlated with more drinking of quinine‐adulterated solutions while high frequency and amount of 5% alcohol consumption at baseline were correlated with being more strongly affected by quinine. Associations between locomotor activity and drinking behavior were observed at the hourly level. These associations reflected changing preferences across experimental phases. Drinking patterns, and specifically solution preference, may offer insights into the presentation of compulsive‐like drinking. The findings provide a preclinical basis for observations from epidemiological studies that link higher risk and burden of alcohol‐related disease to stronger alcohol concentrations and encourage further translational studies to better understand the underlying mechanisms. Understanding the loss of control can improve outcomes in addiction treatment. To examine compulsive‐like drinking, the present study assessed longitudinal drinking behaviour while employing an animal model of relapse including a quinine challenge; addicted rats continue to drink even when the taste of alcohol is made aversive. Findings characterize the response to quinine and suggest a potential link between earlier drinking patterns and eventual compulsive‐like drinking.

As climate change escalates, there is a need for proper planning of future use of water resources. The occurrence of prolonged droughts and fluctuation of weather patterns can lead to serious water scarcity issues. Process integrationtechniques have been widely used for water management in the process plants. This paper extends the insight-based and mathematical programming techniques of process integration to incorporate health aspects in water management. In particular, health quality index is used as a quality metric in considering water recovery in a system of processes. The consideration of health aspects is important for cases involving direct contact of human body with water, such as in water recreational activities. In addition, multi-period planning (MPP) is also considered in this work, where water recovery takes place across different periods. A representative water park case study is used to illustrate the applicability of the proposed method.

Vicilin-buried peptides (VBPs) from edible plants are derived from the N-terminal leader sequences (LSs) of seed storage proteins. VBPs are defined by a common α-hairpin fold mediated by conserved CxxxCx(10–14)CxxxC motifs. Here, peanut and walnut VBPs were characterized as potential mediators of both peanut/walnut allergenicity and cross-reactivity despite their low (∼17%) sequence identity. The structures of one peanut (AH1.1) and 3 walnut (JR2.1, JR2.2, JR2.3) VBPs were solved using solution NMR, revealing similar α-hairpin structures stabilized by disulfide bonds with high levels of surface similarity. Peptide microarrays identified several peptide sequences primarily on AH1.1 and JR2.1, which were recognized by peanut-, walnut-, and dual-allergic patient IgE, establishing these peanut and walnut VBPs as potential mediators of allergenicity and cross-reactivity. JR2.2 and JR2.3 displayed extreme resilience against endosomal digestion, potentially hindering epitope generation and likely contributing to their reduced allergic potential.

In the past two decades, various process integration methods have been proposed for the optimum synthesis of resource conservation networks, for the recovery of energy and material resources such as water, gas, and solvent. In this paper, a mathematical programming framework is proposed for simultaneous optimization of mass exchanger networks(MENs) and direct reuse/recycle networks(DRNs). Both MEN and DRN synthesis are now relatively established fields with numerous methods developed. Note however that there is a lack of work that considers both areas simultaneously. The newly proposed simultaneous optimization method in this work identifies opportunity for a DRN that allows the material waste to be recycled within the MEN, which is the main novelty of this work. The approach is demonstrated with a vinyl acetate monomer production problem. The latter consists of several mass exchange operations, in which an MEN is synthesized. Opportunity to develop an DRN is also identified, which allows its waste to be recycled without regeneration. Another novelty of the work is that, the supply and target compositions in the MEN problem are expressed in terms of mass ratios as the compositions are relatively large. Results show that the integrated network has a total annualized cost that is reduced by 24.9% as compared to the base case configuration, where both networks were solved independently. This shows the importance of considering entire process systems during process synthesis, as opposed to subsystems independently.

People’s ability to evaluate scientific research is important to dealing with the COVID-19 pandemic. STEM educators can use the pandemic to frame instruction of scientific literacy and criticalthinking skills. In a small pilot introductory psychology course taught online in spring 2021, we created jigsaw-style modules organized around real-world applications of psychological research in which students applied results from empirical papers to address current issues and integrated their findings into group projects. In this article, we discuss a module focusing on how children’s development might be impacted by different COVID-19 pandemic school opening policies. We found that students successfully applied empirical results to inform approaches to public policy. Our experience can offer guidance to future STEM instructors incorporating current events into course content to support student learning in a virtual learning environment.

Most methods developed for water minimization for batch processes were reported based on pinch analysis and mathematical programming. In this work, a recently developed P-graph methodology for direct water reuse/recycle is extended for batch water network. The model allows direct water reuse/recycle when water sources and sinks are both located in the same time intervals, or stored for later use through water storage tank. A literature example is used to demonstrate the extended model. The important feature of P-graph is demonstrated through alternative solutions for the batch water network, with different numbers of water storage tanks.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.

Alcohol use disorder (AUD) is closely linked to the brain regions forming the neurocircuitry of addiction. Postmortem human brain tissue enables the direct study of the molecular pathomechanisms of AUD. This study aims to identify these mechanisms by examining differential DNA-methylation between cases with severe AUD (n= 53) and controls (n= 58) using a brain-region-specific approach, in which sample sizes ranged between 46 and 94. Samples of the anterior cingulate cortex (ACC), Brodmann Area 9 (BA9), caudate nucleus (CN), ventral striatum (VS), and putamen (PUT) were investigated. DNA-methylation levels were determined using the Illumina HumanMethylationEPIC Beadchip. Epigenome-wide association analyses were carried out to identify differentially methylated CpG-sites and regions between cases and controls in each brain region. Weighted correlation network analysis (WGCNA), gene-set, and GWAS-enrichment analyses were performed. Two differentially methylated CpG-sites were associated with AUD in the CN, and 18 in VS (q< 0.05). No epigenome-wide significant CpG-sites were found in BA9, ACC, or PUT. Differentially methylated regions associated with AUD case-/control status (q< 0.05) were found in the CN (n= 6), VS (n= 18), and ACC (n= 1). In the VS, the WGCNA-module showing the strongest association with AUD was enriched for immune-related pathways. This study is the first to analyze methylation differences between AUD cases and controls in multiple brain regions and consists of the largest sample to date. Several novel CpG-sites and regions implicated in AUD were identified, providing a first basis to explore epigenetic correlates of AUD.

It is critical to limit global warming to 1.5 °C by the year 2100 to minimize catastrophic impacts. The increased integration of renewable energy, alongside CO2capture and storage(CCS) deployment in energy planning, remains as a key mitigation technique in minimizing climate change impacts. Although renewable energy generation approaches the ideal of a carbon-neutral system, other processes such as fossil fuel-based generation, manufacturing, and transportation are net-carbon positive. Additionally, renewable energy poses challenges such as its sensitivity to environmental conditions, geographical location, and seasonal changes. On the other hand, CCS entails a high capital expenditure, as well as additional operating costs due to parasitic power loss. Therefore, the deployment of negative emission technologies(NETs) as a carbon management option is imperative. The generation of electricity from power plants with the installation of NETs can offset positive emissions from elsewhere in a system. This paper presents an extended graphical technique for the incorporation of NETs during energy planning. The graphical technique that was originally developed for the planning of CCS deployment in power plants is now extended to determine the minimum NET requirement during energy planning. Three examples are solved to illustrate the methodology of the extended graphical technique in determining the minimum NET requirement during energy planning.

Optimum planning of resources is crucial in ensuring business sustainability. In the past decade, several graphical planning tools have been proposed based on process integrationtechniques for the optimum allocation of production resources such as equipment, financial, and human resources. These graphical tools provide useful insights for production planners in allocating resources to fulfill production needs. Nevertheless, graphical tools suffer from inaccuracy problems, in addition to being cumbersome. In this work, algebraic and automated targeting techniques are proposed to overcome the above limitations. The algebraic technique proposed is the numerical equivalent to the graphical targeting tool and can be implemented in spreadsheet software. The automated technique, on the other hand, is conceptually similar to the algebraic technique, but is implemented on an optimization platform. Apart from performing cost optimization, the automated technique can be extended to account for availability and pace of the production resources, which is the main novelty of this work. Doing these would involve tedious iterative steps with both graphical and algebraic techniques. Five examples involving different production resource allocations are solved to demonstrate the newly proposed techniques.

Reduction in carbon emission, minimisation of energy consumption along with on-site power generation and environmental sustainability of industrial processes can be achieved usingtotal site integration(TSI) and combined heat and power(CHP) systems. This paper evaluates cogeneration potential in different TSI methodologies for a dimethyl ether (DME) plant. The evaluation is based on total annual net savings from the CHP system, while considering additional operation and capital costs required for the CHP system. Among the four options for site CHP scheme, the best design option based on revised methodology of Bandyopadhyay et al. 2010. Applied Thermal Engineering (30(1), pp.6–14) achieves the total net savings of 950,874 $/year, with 3% reduction of utility costs and power consumption.

Recent breakthroughs in psychiatric genetics have identified genetic risk factors of yet unknown clinical value. A main ethical principal in the context of psychiatric research as well as future clinical genetic testing is the respect for a person's autonomy to decide whether to undergo genetic testing, and whom to grant access to genetic data. However, experience within the psychiatric genetic research setting has indicated controversies surrounding attitudes toward this ethical principal. This study aimed to explore attitudes concerning the right of individuals to self‐determine testing and disclosure of results, and to determine whether these attitudes are context‐dependent, that is, not directly related to the test result but rather to specific circumstances. N= 160 individuals with major depression or bipolar disorder and n= 29 relatives of individuals with either illness completed an online‐questionnaire assessing attitudes toward genetic testing, genetic research, disclosure of results, incidental findings, and access to psychiatric genetic test results. Generally, the right of the person's autonomy was considered very important, but attitudes varied. For example, half of those who considered that children should have the right to refuse psychiatric genetic testing even against their parents' will, also state that they should be tested upon their parents' wishes. Also, the majority of respondents considered the physician entitled to disregard their stated wishes concerning the disclosure of incidental findings in case of good treatment options. Thus, researchers and clinicians must be aware that attitudes toward psychiatric genetic testing are often mutable and should discuss these prior to testing.

The Logan Hospital Pharmacy Department implemented a training framework (TF) for pharmacy technicians. This study determined whether implementation of a TFfor pharmacy technicians improved knowledge and consistency in pharmacy technician ward‐based services in a large secondary teaching hospital. The study was conducted in two phases. The first phase involved defining competencies and developing a supporting TF. The Competency Handbook for Assistants and Technicians(CHAT) TFconsists of observations, case discussions, feedback sessions and education modules. Questionnaires were developed based on the defined competencies to assess the knowledge component of the TF. The second phase of the study saw the implementation of the TFwithin the department. Practice was observed for each pharmacy technician prior to and following 6–12 months of training against the framework. Implementation of the TFdemonstrated an improvement in both knowledge and consistency of practice. Of the 109 competencies developed, 90 were included for statistical analysis. All participants demonstrated a significant (p < 0.05) improvement in the ward‐based clinical support domain, the core component of advanced‐scope practice. Participants also demonstrated improved performance in their everyday duties. Although all participants trended towards overall improvement in the knowledge domain, this did not reach statistical significance. Implementation of the CHAT TFdelivered improved pharmacy technician knowledge and fostered greater consistency of practice. The results of this pilot study have created a platform for further research into structured development programs and career advancement pathways for pharmacy technicians within Australia.

In this paper, a recently established automated targeting model(ATM) for a heating utility system is extended to integrate the phase separation system in an oil and gas platform to determine its optimum overall cost. A heating medium is used at the oil and gas platform to reduce the viscosity of heavy crude oil from the well and to facilitate the separation process by reducing the size and cost of the separators. The downside of this approach is the additional cost associated with increased heating utility. Therefore, an optimization approach is needed to reconcile the various objectives and to minimize the overall cost. The proposed approach makes use of the pinch analysis-based ATM to find the optimum trade-off between the heating medium system and separation processes. For the ATM, a novel algorithm is introduced to automate the process for temperature sorting and also to locate the heating medium users in their associated temperature intervals. This enables the utility targeting step to be performed despite the changes in temperatures of the heating medium at the crude oil heaters; the latter are located upstream of the crude oil separators. The optimization problem is decomposed into two subproblems. First, the phase separators are sized for optimum cost based on different inlet temperatures. These optimum costs are then associated with the heating utility system by the choice of outlet temperatures at the heaters. Next, the model is solved for overall optimum cost. An industrial case study is used to elucidate the application of the newly proposed approach.

Carbon capture and storage (CCS) reduces carbon dioxide (CO2) emissions by sequestration of captured CO2for long-term storage whereas carbon capture and utilization (CCU) offers resource conservation benefits by displacing the need for extracted CO2from natural sources. The integration of these two results in a carbon capture, utilization, and storage (CCUS) system, which either uses CO2for profitable applications or stores it in the reservoirs. One of the key problems in CCS systems is to optimally match the sources (e.g., CO2captured from fossil-fueled power plants) and the sinks (e.g., available geological reservoirs for storing the captured CO2). In practice, the geological storage sites may be available at different times and have limitations on the maximum CO2storage capacity and the injectivity rate, subject to other geological characteristics. This work proposes an improved pinch analysis-based methodology by simultaneously considering the injectivity constraints and variable availability of all sources and sinks. Two types of CO2storage are considered in this work, that is, sinks with fixed life and sinks with fixed capacity. A new CCUS Mapping Diagramis presented to show the capture of CO2to the individual sinks. Four illustrative examples demonstrate the applicability of the proposed methodology to the CCUS systems in which purity is not a constraint in CO2utilization. In some cases, the improved methodology overcomes the pitfall of the previous method by identifying rigorous CCUS targets.

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment‐resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease‐related common risk variants. Fifty‐one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD‐PRS were calculated for these inpatients and a separate population‐based sample (n= 3,547 healthy; n= 426 self‐reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD‐working group (Cases: n= 59,851; Controls: n= 113,154). MD‐PRS explained a significant proportion of disease status between ECT patients and healthy controls (p= .022, R2= 1.173%); patients showed higher MD‐PRS. MD‐PRS in population‐based depression self‐reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD‐PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment‐resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.

The heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of l-tryptophan oxidation along the kynurenine pathway. IDO1 is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Here we demonstrate that IDO1 is a mammalian nitrite reductase capable of chemically reducing nitrite to nitric oxide (NO) under hypoxia. Ultraviolet–visible absorption and resonance Raman spectroscopy showed that incubation of dithionite-reduced, ferrous–IDO1 protein (FeII–IDO1) with nitrite under anaerobic conditions resulted in the time-dependent formation of an FeII–nitrosyl IDO1 species, which was inhibited by substrate l-tryptophan, dependent on the concentration of nitrite or IDO1, and independent of the concentration of the reductant, dithionite. The bimolecular rate constant for IDO1 nitrite reductase activity was determined as 5.4 M–1s–1(pH 7.4, 23 °C), which was comparable to that measured for myoglobin (3.6 M–1s–1; pH 7.4, 23 °C), an efficient and biologically important mammalian heme-based nitrite reductase. IDO1 nitrite reductase activity was pH-dependent but differed with myoglobin in that it showed a reduced proton dependency at pH >7. Electron paramagnetic resonance studies measuring NO production showed that the conventional IDO1 dioxygenase reducing cofactors, ascorbate and methylene blue, enhanced IDO1’s nitrite reductase activity and the time- and IDO1 concentration-dependent release of NO in a manner inhibited by l-tryptophan or the IDO inhibitor 1-methyl-l-tryptophan. These data identify IDO1 as an efficient mammalian nitrite reductase that is capable of generating NO under anaerobic conditions. IDO1’s nitrite reductase activity may have important implications for the enzyme’s biological actions when expressed within hypoxic tissues.

Optimal synthesis of a heat-integrated water network (HIWN) accounts for the simultaneous conservation of energy and water resources. A significant amount of research work, ranging from complex nonlinear formulations to simplified linear models, has been carried out for the synthesis of HIWNs. The incorporation of interception units leads to additional water and energy conservation but results in nonlinear formulations for heat-integrated water regeneration network (HIWRN) synthesis. This paper proposes a linear mathematical formulation, based on the transshipment model, for the optimization of HIWRNs using distributed interception units. As a result of a reduced number of variables and the absence of nonlinearities, the convergence efficiency is enhanced. The use of distributed interception units allows the regeneration streams to maintain their temperatures, thereby saving a significant amount of energy. A three-stage sequential approach and a simultaneous strategy are proposed for HIWRN synthesis. Although the simultaneous solution strategy provides cost optimal results, the three-stage sequential strategy is preferred in areas dealing with water scarcity and intermittent supply. The solution strategy is applicable to single as well as multiple-contaminant problems for single pass interception units with a fixed outlet and fixed removal ratio (RR). The methodology is demonstrated through literature examples for both types of interception units.

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n= 46,568; African, n= 6,280). Independent, genome-wide significant effects of different ADH1Bvariants were identified in European (rs1229984; P= 9.8 × 10–13) and African ancestries (rs2066702; P= 2.2 × 10–9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Supplemental Digital Content is available in the text.The clinical comorbidity of alcohol dependence (AD) and major depressive disorder (MDD) is well established, whereas genetic factors influencing co-occurrence remain unclear. A recent study using polygenic risk scores (PRS) calculated based on the first-wave Psychiatric Genomics Consortium MDD meta-analysis (PGC-MDD1) suggests a modest shared genetic contribution to MDD and AD. Using a (∼10 fold) larger discovery sample, we calculated PRS based on the second wave (PGC-MDD2) of results, in a severe AD case–control target sample. We found significant associations between AD disease status and MDD-PRS derived from both PGC-MDD2 (most informative P-threshold=1.0, P=0.00063, R2=0.533%) and PGC-MDD1 (P-threshold=0.2, P=0.00014, R2=0.663%) meta-analyses; the larger discovery sample did not yield additional predictive power. In contrast, calculating PRS in a MDD target sample yielded increased power when using PGC-MDD2 (P-threshold=1.0, P=0.000038, R2=1.34%) versus PGC-MDD1 (P-threshold=1.0, P=0.0013, R2=0.81%). Furthermore, when calculating PGC-MDD2 PRS in a subsample of patients with AD recruited explicitly excluding comorbid MDD, significant associations were still found (n=331; P-threshold=1.0, P=0.042, R2=0.398%). Meanwhile, in the subset of patients in which MDD was not the explicit exclusion criteria, PRS predicted more variance (n=999; P-threshold=1.0, P=0.0003, R2=0.693%). Our findings replicate the reported genetic overlap between AD and MDD and also suggest the need for improved, rigorous phenotyping to identify true shared cross-disorder genetic factors. Larger target samples are needed to reduce noise and take advantage of increasing discovery sample size.

Peanut and tree-nut allergies are frequently comorbid for reasons not completely understood. Vicilin-buried peptides (VBPs) are an emerging family of food allergens whose conserved structural fold could mediate peanut/tree-nut co-allergy. Peptide microarrays were used to identify immunoglobulin E (IgE) epitopes from the N-terminus of the vicilin allergens Ara h 1, Ana o 1, Jug r 2, and Pis v 3 using serum from three patient diagnosis groups: monoallergic to either peanuts or cashew/pistachio, or dual allergic. IgE binding peptides were highly prevalent in the VBP domains AH1.1, AO1.1, JR2.1, and PV3.1, but not in AO1.2, JR2.2, JR2.3, and PV3.2 nor the unstructured regions. The IgE profiles did not correlate with diagnosis group. The structure of the VBPs from cashew and pistachio was solved using solution-NMR. Comparisons of structural features suggest that the VBP scaffold from peanuts and tree-nuts can support cross-reactivity. This may help understand comorbidity and cross-reactivity despite a distant evolutionary origin.

IMPORTANCE: Glaucoma represents a major public health challenge in an aging population. The Tanjong Pagar Eye Study reported the prevalence and risk factors of glaucoma in a Singapore Chinese population in 1997, which established the higher rates of blindness in this population. OBJECTIVES: To determine the prevalence and associated risk factors for glaucoma among Chinese adults in Singapore and to compare the results with those of the 1997 study. DESIGN, SETTING, AND PARTICIPANTS: In a population-based survey of 4605 eligible individuals, we selected 3353 Chinese adults 40 years or older from the southwestern part of Singapore. Participants underwent examination at a single tertiary care research institute from February 9, 2009, through December 19, 2011. EXPOSURES: All participants underwent slitlamp ophthalmic examination, applanation tonometry, measurement of central corneal thickness, gonioscopy, and a dilated fundus examination. MAIN OUTCOMES AND MEASURES: Glaucoma as defined by the International Society of Geographical and Epidemiological Ophthalmology guidelines and age-standardized prevalence estimates computed as per the 2010 Singapore Chinese census. Blindness was defined as logMAR visual acuity of 1.00 (Snellen equivalent, 20/200 or worse). RESULTS: Of the 3353 respondents, 134 (4.0%) had glaucoma, including primary open-angle glaucoma (POAG) in 57 (1.7%), primary angle-closure glaucoma (PACG) in 49 (1.5%), and secondary glaucoma in 28 (0.8%). The age-standardized prevalence (95% CI) of glaucoma was 3.2% (2.7%-3.9%); POAG, 1.4% (1.1%-1.9%); and PACG, 1.2% (0.9%-1.6%). In a multivariate model, POAG was associated with being older and male and having a higher intraocular pressure. Of the 134 participants with glaucoma, 114 (85.1%; 95% CI, 78.1%-90.1%) were not aware of their diagnosis. Prevalence (95% CI) of blindness caused by secondary glaucoma was 14.3% (5.7%-31.5%), followed by 10.2% (4.4%-21.8%) for PACG and 8.8% (3.8%-18.9%) for POAG. We could not identify a difference in the prevalence of glaucoma compared with the 3.2% reported in 1997 (difference, −0.04%; 95% CI, −1.2 to 1.2; P = .97). CONCLUSIONS AND RELEVANCE: The prevalence of glaucoma among Singapore Chinese likely ranges from 2.7% to 3.9%, with secondary glaucoma being the most visually debilitating type. We could not identify a difference compared with previous studies approximately 12 years earlier. We report a high proportion of previously undiagnosed disease, suggesting the need to increase public awareness of this potentially blinding condition.

In situ testing of a timber Warren truss building and laboratory testing of four truss joints typical of those found in a Warren truss building are carried out over a span of five years. The overall objective of this research program is to investigate the behavior of many aging and deteriorating timber Warren truss buildings built in early 1940. Field testing involve loading 16 full size timber trusses to failure to determine their loadcarrying capacities and the effects of joint reinforcement on the behavior of the trusses. Laboratory testings are performed on the four biggest joints of a Warren truss in several conditions: cut from an existing truss, manufactured with new wood, unreinforced condition, reinforced condition using gusset plates, and reinforced condition by means of prestressing. This paper presents an overview of the research program and some of the findings regarding the effectiveness of the joint strengthening schemes considered.

Thermal comfort field experiments were conducted in Singapore in both naturally ventilated highrise residential buildings and air conditioned office buildings. Each of the 818 questionnaire responses was made simultaneously with a detailed set of indoor climatic measurements, and estimates of clothing insulation and metabolic rate. Results for the air conditioned sample indicated that office buildings were overcooled, causing up to one-third of their occupants to experience cool thermal comfort sensations. These observations in air conditioned buildings were broadly consistent with the ISO, ASHRAE and Singapore indoor climatic standards. Indoor climates of the naturally ventilated apartments during the day and early evening were on average three degrees warmer than the ISO comfort standard prescriptions, but caused much less thermal discomfort than expected. Discrepancies between thermal comfort responses in apartment blocks and office buildings are discussed in terms of contemporary perceptual theory.

Analysis of the postshift toluene levels in the blood of 50 assembly line workers indicates that toluene levels in blood were correlated with the time-weighted average (TWA) exposure levels of the same day (r=0.90). Toluene concentrations in 10 laboratory technicians not exposed to toluene at their work gave an average level of 0.002 µg/mL of blood. Significant levels of residual toluene were found in the preshift blood of workers exposed to 57 to 146 ppm of toluene as compared to the unexposed. The blood toluene values determined from capillary blood taken from finger tips are higher than the reported values from venous blood. The method described is useful for large-scale screening and epidemiological surveys.

A study was undertaken to examine the relationship between exposure of workers to toluene in the work environment and biological indicators of toluene exposure. The biological indicators studied were toluene in expired air, toluene in blood obtained by the finger prick method, and urinary hippuric acid. The study was undertaken in a factory in Singapore that manufactures speakers for audio systems. A total of 86 female workers exposed to toluene at the workplace and a control group of workers not exposed to toluene were examined. All of them were teetotalers, were nonsmokers, and gave no history of chronic drug usage. The 8-hr time-weighted average exposure level of toluene ranged from 1.6 ppm to 263 ppm. The study showed the expected toluene levels in finger prick blood was 1.4 µ/mL after an 8-hr exposure to 100 ppm of toluene. Toluene concentration in expired air of 16 ppm after an 8-hr exposure to 100 ppm compared favorably with other studies. The toluene in blood/expired air ratio was observed to be lower than in other studies. In this study, the expected urinary hippuric acid level for a 100-ppm exposure to toluene was 2.7 g/g creatinine. This level is higher than that recorded in other studies. The results showed that at low levels of toluene, urinary hippuric acid is not a valuable indicator of exposure. Toluene in expired air is the most reliable biological indicator of exposure to toluene.

The rat vasopressin gene contains two transcriptional promoters; the activity of one is confined to the hypothalamus, while the other is testis specific. To define the sequences mediating the cell-specific expression of the vasopressin gene, we introduced rat vasopressin transgenes into the rat germ line. Neither transgene 1.5-Vβgal-0.2, which consists of the entire vasopressin structural gene containing a 3 kbp β-galactosidase reporter element in exon III, flanked by 1.5 kbp upstream of the start of hypothalamic transcription and 0.2 kbp downstream of the polyadenylation site, nor transgene 3-Vβgal-0.2, which consists of the entire VP structural gene containing a 3 kbp β-galactosidase reporter element in exon III, flanked by 3 kbp upstream of the start of hypothalamic transcription and 0.2 kbp downstream of the polyadenylation site, were expressed in the hypothalamus. This contrasts with a previously described transgene consisting of the rat vasopressin structural gene containing a reporter in exon III, flanked by 5 kbp of upstream and 3 kbp of downstream sequences, which is expressed in vasopressinergic hypothalamic neurones. Both the 3-Vβgal-0.2 and 1.5-Vβgal-0.2 transgenes were expressed in testicular germ cells using a promoter located within the α-galactosidase reporter element. Transgene RNA was most abundant during the late stages of meiosis. Rats bearing vasopressin-β-galactosidase transgenes provide new models for the study of the mechanisms whereby an epigenetic choice is made between the use of a germ cell or a somatic promoter, and the stage-specific transcriptional regulation of a germ cell promoter during spermatogenesis.

Antigenic cross-reaction has been demonstrated between homogenates of intestine taken from fetal mice and suspensions of a Bacteriodesspecies isolated from the large intestines of normal adult mice. This observation provides an explanation for the lack of immunological response observed in mice after antigenic stimulation with this member of the normal autochthonous intestinal flora of these animals.

Summary Hair samples from three groups of occupationally exposed subjects were analyzed for their lead (Pb), manganese (Mn) and mercury (Hg) contents. For lead (number of subjects, n=209), the hair Pb ranged from 0.93 to 3527 µg/g (geometric mean, GM=641) and blood Pb from 33.3 to 774 µg/l (GM=341); for manganese (n=38), the hair Mn ranged from 0.20 to 52.97 µg/g (GM=2.66) and urine Mn ranged from 1.70 to 17.9 µg/l (GM=5.56); and for mercury (n=85), the hair Hg from 1.79 to 12.8 µg/g (GM=5.09) and the blood Hg from 0.63 to 57.3 µg/l (GM=10.9). The hair Pb was significantly (P<0.0001) correlated to blood Pb (r=0.85); the hair Mn to urinary Mn (r=0.45); and the hair Hg to blood Hg (r=0.53). The average metal content at the distal end was not significantly (P>0.05) different from that of proximal end. The GM levels for the distal end were 223 µg/g (95% CI 152–347) and 2.26 (95% CI 0.97–5.29); and those for the proximal end were 186 (95% CI 97–261) and 1.18 (95% CI 0.54–2.58) for Pb and Mn respectively. However, linear regression analysis of hair metal levels in the proximal end with respect to those in the distal end after logarithmic transformation showed that hair Pb in the proximal end was related to hair Pb in the distal end with a slope of 0.95 (95% Cl 0.89–1.01) whereas hair Mn in the proximal end was related to that of the distal end with a slope of only 0.52 (95% CI 0.13–0.91), reflecting the relatively constant Pb exposure as compared to the dropping Mn exposure in recent years. Metals in hair are suitable biological indicators for exposure and the distribution along the different segments of hair strands reflects the time history of exposure.

Based on agglutination, complement fixation, bactericidal, and opsonization tests, it is evident that suspensions of a Bacteroidessp. isolated from the mouse intestine and given by parenteral routes do not initiate antibody formation in mice. Rats also respond poorly to the antigenic stimulus. In contrast, suspensions of other bacterial species isolated from the rodent intestine are highly immunogenic. Furthermore, high titers of antibody are produced in rabbits, guinea pigs, and sheep after parenteral injection of the Bacteroidessuspensions. Marked differences in the absolute and relative numbers of Bacteroidesin the intestinal contents of rodents and the latter three animal species have been demonstrated. It is proposed that the immunological unresponsiveness of rodents to this organism is related to its existence as a member of the autochthonous microflora in these animals.

Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.

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