Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research

HEN Retrofit Solution in an AVCODU by Using Process Heat Integration and Process Simulation Methodologies

The recent energy and environmental issues urge the need to revamp the existing plants in order to minimize the energy requirements and consequently decreases environmental pollution. This paper represents an application of methods for performance analysis of existing processes and finding of retrofit solutions through the application of techniques for process modeling and simulation and process integration. An in atmospheric and in vacuum conditions crude oil distillation unit (AVCODU) from a typical refinery [Kaes G., 2002] is considered as the case study for above mentioned scope of this work. Various Heat exchanger Networks (HENs) has been developed by applying the process heat integration (HI) pinch approach. However, it has been estimated that 16.2 MW hot utility and 16.22 MW of cold utility can be saved in a year by revamping of pre-heating train of AVCODU. Furthermore, capital cost of revamping can be recovered within 2.3 year of plant operation. Keywords: oil atmospheric/vacuum distillation; heat integration, pinch points methodology, capital/operating costs, heat exchanger network (HEN) topology, find a HEN retrofit candidate, adopt a HEN retrofit solution from the candidates group One of the major energy demands within AVCODU process in refineries comes from the need to heat the crude feedstock upstream of the crude distillation column to obtain the desired flash temperatures and adequate characteristics and yield of distillation products. Energy requirement can be minimized by adopting process scheme ensuring an advanced heat recovery inside that process. Process modeling, simulation and HI techniques help process engineers for finding design solution to make process in refinery to be more efficient in energy use. Conventionally, the HI was achieved by experience of operation and engineering insights. The best design was chosen by the set of case studies. However, in late 70 and early 80, the development of pinch analysis (PA) methodology Problem description and methodology Process modeling and simulation of existing plant is the first step of procedure to finding solution for pre-heating train revamp. Process data is extracted by process modeling and simulation or/and from indication of instrumentation serving to process control of the existing plant. The said data is then used for setting the performance targets by using pinch approach. Then Process * email: [email protected], Tel. + 4021-402 3867; [email protected] modifications, network design, design evolution and new process simulation are the next steps to develop the best energy efficient pre-heating train. Case study The refinery's AVCODU is processing 85000 barrels / day light Arabian crude oil. Process configuration, given in Pre-heating train configuration, given in figure 2 had eleven shell and tube heat exchangers that heated the crude oil by exchanging heat with product streams from distillation columns (overhead gases of atmospheric column, kerosene, diesel, Kerosene P/A, Diesel P/A, Heavy Vacuum Gas Oil (HVGO) and residue of vacuum column). The said HEN ensure the increasing of the crude oil temperature from 38 o C (approx) to 245.9 o C (approx) in the existing process plant. Four types of utilities are used in the existing plant. Two hot utilities i.e. medium steam (187 o C) and flue gas while two cold utilities i.e. cooled air and cooling water are used in the existing process plant. Flue gas furnace is used to heat the crude oil (from 245.9 to 343

Preservation and Recovery of Metal-Tolerant Fungi from Industrial Soil and Their Application to Improve Germination and Growth of Wheat

Heavy metals contaminate soil and adversely affect plant growth. These soils contain different fungi and bacteria which exhibit metal tolerance and work as bioremediation agents to detoxify polluted soils. In the present study, polluted soil samples were collected to estimate the contamination of copper (Cu) and cadmium (Cd). From this contaminated soil, metal tolerant fungi were isolated and characterized. Copper and cadmium were found in a range of 190.2–300.4 mg/kg and 46.8–56.1 mg/kg, respectively. For the isolation of metal tolerant fungi, soil dilutions were made in water and inoculated on potato dextrose agar (PDA) media. Fungal growth was observed on PDA and successive screening resulted in the isolation of four multi-metal tolerant fungal species, including Penicillim oxalicum, Fusarium solani, Aspergillus niger and Trichoderma harzianum. Sequencing of 18S rRNA genes of isolated fungi also efficiently identified them. To reveal minimum inhibitory concentrations (MIC), these fungi were exposed to increasing concentrations of cadmium and copper chlorides (100 to 1000 ppm) and a variable MIC range of 400 ppm to 1000 ppm was estimated. Based on tolerance index analysis, F. solani was found to be resistant at 1 mM copper, while P. oxalicum was the most tolerant species under cadmium stress. F. solani and P. oxalicum demonstrated the highest biosorption capacity of Cu and Cd, respectively. Both metals negatively affected wheat seedlings in a pot experiment, while the treatment of both F. solani and P. oxalicum positively influenced the germination and growth of wheat. Based on these observations, it could be inferred that F. solani and P. oxalicum can be used for the myco-remediation of Cu and Cd, respectively

Preservation and Recovery of Metal-Tolerant Fungi from Industrial Soil and Their Application to Improve Germination and Growth of Wheat

Heavy metals contaminate soil and adversely affect plant growth. These soils contain different fungi and bacteria which exhibit metal tolerance and work as bioremediation agents to detoxify polluted soils. In the present study, polluted soil samples were collected to estimate the contamination of copper (Cu) and cadmium (Cd). From this contaminated soil, metal tolerant fungi were isolated and characterized. Copper and cadmium were found in a range of 190.2–300.4 mg/kg and 46.8–56.1 mg/kg, respectively. For the isolation of metal tolerant fungi, soil dilutions were made in water and inoculated on potato dextrose agar (PDA) media. Fungal growth was observed on PDA and successive screening resulted in the isolation of four multi-metal tolerant fungal species, including Penicillim oxalicum, Fusarium solani, Aspergillus niger and Trichoderma harzianum. Sequencing of 18S rRNA genes of isolated fungi also efficiently identified them. To reveal minimum inhibitory concentrations (MIC), these fungi were exposed to increasing concentrations of cadmium and copper chlorides (100 to 1000 ppm) and a variable MIC range of 400 ppm to 1000 ppm was estimated. Based on tolerance index analysis, F. solani was found to be resistant at 1 mM copper, while P. oxalicum was the most tolerant species under cadmium stress. F. solani and P. oxalicum demonstrated the highest biosorption capacity of Cu and Cd, respectively. Both metals negatively affected wheat seedlings in a pot experiment, while the treatment of both F. solani and P. oxalicum positively influenced the germination and growth of wheat. Based on these observations, it could be inferred that F. solani and P. oxalicum can be used for the myco-remediation of Cu and Cd, respectively

Self-reported health and smoking status, and body mass index: a case-control comparison based on GEN SCRIP (GENetics of SChizophRenia In Pakistan) data

Introduction Individuals with schizophrenia are at a high risk of physical health comorbidities and premature mortality. Cardiovascular and metabolic causes are an important contributor. There are gaps in monitoring, documenting and managing these physical health comorbidities. Because of their condition, patients themselves may not be aware of these comorbidities and may not be able to follow a lifestyle that prevents and manages the complications. In many low-income and middle-income countries including Pakistan, the bulk of the burden of care for those struggling with schizophrenia falls on the families.Objectives To determine the rate of self-reported physical health disorders and risk factors, like body mass index (BMI) and smoking, associated with cardiovascular and metabolic disorders in cases of schizophrenia compared with a group of mentally healthy controls.Design A case-controlled, cross-sectional multicentre study of patients with schizophrenia in Pakistan.Settings Multiple data collection sites across the country for patients, that is, public and private psychiatric OPDs (out patient departments), specialised psychiatric care facilities, and psychiatric wards of teaching and district level hospitals. Healthy controls were enrolled from the community.Participants We report a total of 6838 participants’ data with (N 3411 (49.9%)) cases of schizophrenia compared with a group of healthy controls (N 3427 (50.1%)).Results BMI (OR 0.98 (CI 0.97 to 0.99), p=0.0025), and the rate of smoking is higher in patients with schizophrenia than in controls. Problems with vision (OR 0.13 (0.08 to 0.2), joint pain (OR 0.18 (0.07 to 0.44)) and high cholesterol (OR 0.13 (0.05 to 0.35)) have higher reported prevalence in controls. The cases describe more physical health disorders in the category ‘other’ (OR 4.65 (3.01 to 7.18)). This captures residual disorders not listed in the questionnaire.Conclusions Participants with schizophrenia in comparison with controls report more disorders. The access in the ‘other’ category may be a reflection of undiagnosed disorders