The surgical pathology laboratory in Mwanza, Tanzania: A survey on the reproducibility of diagnoses after the first years of autonomous activity

Background: In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant. Results: Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 (P = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses). Conclusion: This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions

Pathological Features of Breast Cancer seen in Northwestern Tanzania: A Nine Years Retrospective Study.

Breast cancer is more common in Western Countries compared to African populations. However in African population, it appears that the disease tends to be more aggressive and occurring at a relatively young age at the time of presentation. The aim of this study was to describe the trend of Breast Cancer in Northwestern Tanzania. This was a retrospective study which involved all cases of breast cancer diagnosed histologically at Bugando Medical Center from 2002 to 2010. Histological results and slides were retrieved from the records in the Pathology department, clinical information and demographic data for patients were retrieved from surgical wards and department of medical records. Histology slides were re-evaluated for the histological type, grade (By modified Bloom-Richardson score), and presence of necrosis and skin involvement. Data was entered and analyzed by SPSS computer software version 15. There were 328 patients histologically confirmed to have breast cancer, the mean age at diagnosis was 48.7 years (+/- 13.1). About half of the patients (52.4%) were below 46 years of age, and this group of patients had significantly higher tendency for lymph node metastasis (p = 0.012). The tumor size ranged from 1 cm to 18 cm in diameter with average (mean) of 5.5 cm (+/- 2.5), and median size of 6 cm. Size of the tumor (above 6 cm in diameter) and presence of necrosis within the tumor was significantly associated with high rate of lymph node metastasis (p = 0.000). Of all patients, 64% were at clinical stage III (specifically IIIB) and 70.4% had lymph node metastasis at the time of diagnosis. Only 4.3% of the patients were in clinical stage I at the time of diagnosis. Majority of the patients had invasive ductal carcinoma (91.5%) followed by mucinous carcinoma (5.2%), Invasive lobular carcinoma (3%) and in situ ductal carcinoma (0.3%). In all patients, 185 (56.4%) had tumor with histological grade 3. Breast cancer in this region show a trend towards relative young age at diagnosis with advanced stage at diagnosis and high rate of lymph node metastasis. Poor Referral system, lack of screening programs and natural aggressive biological behavior of tumor may contribute to advanced disease at the time of diagnosis

Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.

Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children

Allergic Rhinitis and its Associated Co-Morbidities at Bugando Medical Centre in Northwestern Tanzania; A Prospective Review of 190 Cases.

Allergic rhinitis is one of the commonest atopic diseases which contribute to significant morbidity world wide while its epidemiology in Tanzania remains sparse. There was paucity of information regarding allergic rhinitis in our setting; therefore it was important to conduct this study to describe our experience on allergic rhinitis, associated co-morbidities and treatment outcome in patients attending Bugando Medical Centre. This was descriptive cross-sectional study involving all patients with a clinical diagnosis of allergic rhinitis at Bugando Medical Centre over a three-month period between June 2011 and August 2011. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 17.0. A total of 190 patients were studied giving the prevalence of allergic rhinitis 14.7%. The median age of the patients was 8.5 years. The male to female ratio was 1:1. Adenoid hypertrophy, tonsillitis, hypertrophy of inferior turbinate, nasal polyps, otitis media and sinusitis were the most common co-morbidities affecting 92.6% of cases and were the major reason for attending hospital services. Sleep disturbance was common in children with adenoids hypertrophy (χ2 = 28.691, P = 0.000). Allergic conjunctivitis was found in 51.9%. The most common identified triggers were dust, strong perfume odors and cold weather (P < 0.05). Strong perfume odors affect female than males (χ2 = 4.583, P = 0.032). In this study family history of allergic rhinitis was not a significant risk factor (P =0.423). The majority of patients (68.8%) were treated surgically for allergic rhinitis co morbidities. Post operative complication and mortality rates were 2.9% and 1.6% respectively. The overall median duration of hospital stay of in-patients was 3 days (2 - 28 days). Most patients (98.4%) had satisfactory results at discharge. The study shows that allergic rhinitis is common in our settings representing 14.7% of all otorhinolaryngology and commonly affecting children and adolescent. Sufferers seek medical services due to co-morbidities of which combination of surgical and medical treatment was needed. High index of suspicions in diagnosing allergic rhinitis and early treatment is recommended

Human performance and strategies while solving an aircraft routing and sequencing problem: an experimental approach

As airport resources are stretched to meet increasing demand for services, effective use of ground infrastructure is increasingly critical for ensuring operational efficiency. Work in operations research has produced algorithms providing airport tower controllers with guidance on optimal timings and sequences for flight arrivals, departures, and ground movement. While such decision support systems have the potential to improve operational efficiency, they may also affect users’ mental workload, situation awareness, and task performance. This work sought to identify performance outcomes and strategies employed by human decision makers during an experimental airport ground movement control task with the goal of identifying opportunities for enhancing user-centered tower control decision support systems. To address this challenge, thirty novice participants solved a set of vehicle routing problems presented in the format of a game representing the airport ground movement task practiced by runway controllers. The games varied across two independent variables, network map layout (representing task complexity) and gameplay objective (representing task flexibility), and verbal protocol, visual protocol, task performance, workload, and task duration were collected as dependent variables. A logistic regression analysis revealed that gameplay objective and task duration significantly affected the likelihood of a participant identifying the optimal solution to a game, with the likelihood of an optimal solution increasing with longer task duration and in the less flexible objective condition. In addition, workload appeared unaffected by either independent variable, but verbal protocols and visual observations indicated that high-performing participants demonstrated a greater degree of planning and situation awareness. Through identifying human behavior during optimization problem solving, the work of tower control can be better understood, which, in turn, provides insights for developing decision support systems for ground movement management

Cryptic speciation and chromosomal repatterning in the South African climbing mice Dendromus (Rodentia, Nesomyidae)

We evaluate the intra- and interspecific diversity in the four South African rodent species of the genus Dendromus. The molecular phylogenetic analysis on twenty-three individuals have been conducted on a combined dataset of nuclear and mitochondrial markers. Moreover, the extent and processes underlying chromosomal variation, have been investigated on three species by mean of G-, C-bands, NORs and Zoo-FISH analysis. The molecular analysis shows the presence of six monophyletic lineages corresponding to D. mesomelas, D. mystacalis and four lineages within D. cfr. melanotis with high divergence values (ranges: 10.6% – 18.3%) that raises the question of the possible presence of cryptic species. The first description of the karyotype for D. mesomelas and D. mystacalis and C- and G- banding for one lineage of D. cfr. melanotis are reported highlighting an extended karyotype reorganization in the genus. Furthermore, the G-banding and Zoo-FISH evidenced an autosome-sex chromosome translocation characterizing all the species and our timing estimates this mutation date back 7.4 mya (Late Miocene). Finally, the molecular clock suggests that cladogenesis took place since the end of Miocene to Plio-Pleistocene, probably due to ecological factors, isolation in refugia followed by differential adaptation to the mesic or dry habitat

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10  × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD

A combination of the immunohistochemical markers CK7 and SATB2 is highly sensitive and specific for distinguishing primary ovarian mucinous tumors from colorectal and appendiceal metastases

This study is supported by research funds from Cancer Research Society of Canada (19319). NSM is supported by the NSW Ministry of Health and UNSW Sydney under the NSW Health PhD Scholarship Program, and the Translational Cancer Research Network, a translational cancer research center program funded by the Cancer Institute NSW. The Gynaecological Oncology Biobank at Westmead was funded by Cancer Institute NSW (12/RIG/1–17 and 15/RIG/1–16) and the National Health and Medical Research Council of Australia (ID310670, ID628903). FM is funded by University of Pittsburgh School of Medicine Dean's Faculty Advancement Award. The HOPE study is funded by: US National Cancer Institute (K07-CA80668, P50-CA159981, R01CA095023), US Army Medical Research and Materiel Command (DAMD17–02–1–0669) and NIH/National Center for Research Resources/General Clinical Research Center (MO1- RR000056). KS is funded by the Swedish Cancer foundation. The Generations Study thank Breast Cancer Now, the Institute of Cancer Research and Ovarian Cancer Action for support and funding. The ICR acknowledge NHS funding to the NIHR Biomedical Research Centre. Tissue samples for GER were provided by the tissue bank of the National Center for Tumor Diseases (NCT, Heidelberg, Germany) in accordance with the regulations of the tissue bank and the approval of the ethics committee of the University of Heidelberg. The Health Science Alliance (HSA) Biobank acknowledges the UNSW Biorepository, UNSW Sydney, Australia. We thank Shuhong Liu, Young Ou, and Deon Richards for immunohistochemical stains, and Thomas Kryton, BFA, digital imaging specialist for Alberta Public Lab for creating the figures. We especially thank all the study participants, health care staff and data providers internationally who have made this research possible