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

Traditional healers working with primary care and mental health for early intervention in psychosis in young persons: protocol for the feasibility cluster randomised controlled trial

Objectives In low/middle-income countries (LMICs), more than half of patients with first-episode psychosis initially seek treatment from traditional and religious healers as their first care. This contributes to an excessively long duration of untreated psychosis (DUP). There is a need for culturally appropriate interventions to involve traditional and spiritual healers to work collaboratively with primary care practitioners and psychiatrists through task-shifting for early detection, referral and treatment of first episode of psychosis. Methods To prevent the consequences of long DUP in adolescents in LMICs, we aim to develop and pilot test a culturally appropriate and context-bespoke intervention. Traditional HEalers working with primary care and mental Health for early interventiOn in Psychosis in young pErsons (THE HOPE) will be developed using ethnographic and qualitative methods with traditional healers and caregivers. We will conduct a randomised controlled cluster feasibility trial with a nested qualitative study to assess study recruitment and acceptability of the intervention. Ninety-three union councils in district Peshawar, Pakistan will be randomised and allocated using a 1:1 ratio to either intervention arm (THE HOPE) or enhanced treatment as usual and stratified by urban/rural setting. Data on feasibility outcomes will be collected at baseline and follow-up. Patients, carers, clinicians and policymakers will be interviewed to ascertain their views about the intervention. The decision to proceed to the phase III trial will be based on prespecified stop–go criteria. Ethics and dissemination Ethical approval has been obtained from Keele University Ethical Review Panel (ref: MH210177), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/IG/001005) and National Bioethics Committee Pakistan (ref no. 4-87/NBC-840/22/621). The results of THE HOPE feasibility trial will be reported in peer-reviewed journals and academic conferences and disseminated to local stakeholders and policymakers. Trial registration number ISRCTN75347421

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

COST OF PRODUCTION, GROSS RETURN AND NET PROFIT IN COMMERCIAL EGG PRODUCTION

The present study was carried out in Chakwal, Pakistan by collecting data from randomly selected 109 flocks to investigate cost of production, gross return and net profit per layer. Majority of the buildings in the study area were rented therefore, rent per layer was added to the total cost of production instead of depreciation on building and equipments. Overall total cost of production, gross return and net profit per layer was Rs. 393.88 ± 5.36, 432.14 ± 8.01 and 38.26 ± 6.66, respectively. Rate of return over the invested capital was 27%. Mean feed cost per layer was Rs. 302.23 ± 5.01, including Rs. 10.27 ± 0.24, 29.19 ± 0.42 and 262.77 ± 5.08 for starter, grower and layer ration, respectively. Feed cost was the major component contributing 76.73% to the total cost of production. Average cost of labor, day-old chick, building rent, vaccination, therapy, miscellaneous item, electricity, bedding material and transportation was Rs. 19.90 ± 0.45, 19.75 ± 0.05, 16.25 ± 0.26, 12.80 ± 0.10, 10.90 ± 2.32, 4.35 ± 0.09, 3.15 ± 0.07, 2.65 ± 0.09 and 1.90 ± 0.08, respectively, contributing 5.05, 5.01, 4.13, 3.25, 2.77, 1.10, 0.80, 0.67 and 0.48 % to the total cost of production. Gross return from the sale of marketable eggs, culled eggs, spent/culled bird, empty bags and manure was Rs. 388.84 ± 7.91, 3.85 ± 0.01, 35.80 ± 0.23, 2.20 ± 0.04 and 1.45 ± 0.01, respectively, contributing 89.98, 0.89, 8.28, 0.51 and 0.34% to the total return. Determining the effect of different parameters on the cost of production and net profit, large flocks, Hisex strain, brood-grow and lay system of rearing, good hygienic conditions of the farm, normal stocking rate and cage system of housing wee found to give maximum gross return as well as net profit

Proactive Caching at the Edge Leveraging Influential User Detection in Cellular D2D Networks

Caching close to users in a radio access network (RAN) has been identified as a promising method to reduce a backhaul traffic load and minimize latency in 5G and beyond. In this paper, we investigate a novel community detection inspired by a proactive caching scheme for device-to-device (D2D) enabled networks. The proposed scheme builds on the idea that content generated/accessed by influential users is more probable to become popular and thus can be exploited for pro-caching. We use a Clustering Coefficient based Genetic Algorithm (CC-GA) for community detection to discover a group of cellular users present in close vicinity. We then use an Eigenvector Centrality measure to identify the influential users with respect to the community structure, and the content associated to it is then used for pro-active caching using D2D communications. The numerical results show that, compared to reactive caching, where historically popular content is cached, depending on cache size, load and number of requests, up to 30% more users can be satisfied using a proposed scheme while achieving significant reduction in backhaul traffic load

Blood First Edition paper

Key Points • There is 100% concordance in the cytogenetic and mutation profile between PB and BM in myelodysplastic syndrome. Recent studies have shown that more than 80% of bone marrow (BM) samples from patients with myelodysplastic syndrome (MDS) harbor somatic mutations and/or genomic aberrations, which are of diagnostic and prognostic importance. We investigated the potential use of peripheral blood (PB) and serum to identify and monitor BM-derived genetic markers using high-resolution single nucleotide polymorphism array (SNP-A) karyotyping and parallel sequencing of 22 genes frequently mutated in MDS. This pilot study showed a 100% SNP-A karyotype concordance and a 97% mutation concordance between the BM and PB. In contrast, mutation analysis using Sanger sequencing of PB and serum-derived DNA showed only 65% and 42% concordance to BM, respectively. Our results show the potential utility of PB as a surrogate for BM for MDS patients, thus avoiding the need for repeated BM aspirates particularly in elderly patients and those with fibrotic or hypocellular marrows. (Blood. 2013;122(4):567-570) Introduction The myelodysplastic syndromes (MDSs) are clonal disorders of hematopoiesis that occur predominantly in the elderly (median age 72 years) and are characterized by morphologic dysplasia, ineffective hematopoiesis, peripheral blood (PB) cytopenias, chromosomal aberrations, and propensity to myeloid leukemic transformation. The advent of high-throughput and high-resolution techniques for genetic analysis has shown that more than 80% of MDS patients harbor somatic mutations and/or genomic aberrations in their bone marrow (BM), which provide pathogenetic as well as diagnostic and prognostic insights into this disease. 1-4 Frequent BM aspirates may be required for morphological Study design Genomic DNA from PB and BM was extracted (Qiagen) from frozen cell pellets and 100 ng was whole genome amplified (WGA; Qiagen), both per manufacturer's protocols. Serum DNA was purified from 200 mL of serum using a modified sodium iodide/Triton-based lysis followed by isopropanol precipitation as described. 12 Affymetrix SNP 6.0 array (SNP-A) karyotyping and 454-PS of all exons of DNMT3a, RUNX1, CEBPa, TP53, EZH2, and ZRSR2 and mutation "hot spots" for NPM1, FLT3, ASXL1, IDH1, IDH2, MPL, JAK2, BRAF, cCBL, NRAS, KRAS, C-KIT, SF3B1, SRSF2, and U2AF35 were performed and analyzed as previously described. 13,14 TET2 was analyzed using Sanger sequencing. Independent validation for all mutations was performed using Sanger sequencing of unamplified genomic DNA. Polymerase chain reaction (PCR) conditions for serum were identical to those for PB; however, a second 10-cycle PCR reaction using nested primers (US1-GTAGTGCGATGGCCAGT, US2-CAGTGTGCAGCGATGAC) was required to provide adequate amplicon yield for Sanger sequencing. The study was approved by the local research ethics committee under project 0033 and conducted in accordance with the Declaration of Helsinki. Results and discussion Karyotype analysis Karyotype aberrations were assessed using SNP-A on PB samples from 31 MDS patients, from whom metaphase cytogenetics (MC) and BM SNP-A karyotypes were available. These consisted of th

Utility of peripheral blood for cytogenetic and mutation analysis in myelodysplastic syndrome

Key Points There is 100% concordance in the cytogenetic and mutation profile between PB and BM in myelodysplastic syndrome.</jats:p

Plant Growth Promoting Rhizobacteria (PGPR) and Arbuscular Mycorrhizal Fungi Combined Application Reveals Enhanced Soil Fertility and Rice Production

Rice (Oryza sativa L.) is an important crop that is grown worldwide to supply the world’s expanding food demand. In the current study, the effects of plant growth-promoting rhizobacteria (PGPR) and Arbuscular mycorrhizal fungi (AMF) on soil fertility and rice growth were explored. Rice plants were inoculated to evaluate how AMF fungi and PGPR affect various aspects of soil and plants, implicating abiotic stress tolerances. The experiment was carried out in a completely randomized design with three replicates under the controlled conditions. Results depicted that the plants that were inoculated with a mixture of AMF and PGPR had better yields and nutritional concentrations, while both AMF and PGPR lowered soil pH and organic matter differently. Similarly, AMF and PGPR treatments significantly increased the amount of N, P, K, and B in the post-harvest soil. The PGPR-inoculated plants had a 10–40% higher buildup of N in their tissues. Similarly, when they were compared with non-infected plants, AMF-inoculated treatments demonstrated a greater N accumulation in the rice tissue. The maximum P content in plant tissues was 0.149% in PGPR5-infected plants, either alone or in combination with AMF. In T12, AMF + PGPR5 inoculated rice plants, the maximum K uptake was 1.98%, which was 54% higher than the control treatment. The sole application of AMF raised K buildup in rice tissues by 38% compared with the control treatment. The improved productivity of plants with AMF and PGPR (especially with PGPR5) was attributed to the increased availability of nutrients in the soil. As a result, rice plant growth, yield, and essential element uptakes were boosted significantly. The present study’s results suggested using the combined application of AMF + PGPR5 for improving the rice yield and for sustaining the soil health