Integration of multiple geospatial applications and intelligence for responding to COVID-19 in Ghana

Objective: We describe the use of integrated geospatial applications for the provision of access to timely and accurate data on samples, visualisation of Spatio-temporal patterns of cases and effective communication between field sample collectors, testing laboratories, Regional Health directors and Government Decision Makers.Design: This study describes how an integrated geospatial platform based on case location and intelligence was developed and used for effective COVID-19 response during the initial stages of COVID-19 in Ghana.Data Source: Collector for ArcGIS, ArcGIS Survey123Main outcome measure: successful development and deployment of integrated geospatial applications and analytics.                                                              Results: The Collector for ArcGIS app was customised to collect COVID-19 positive cases location information. Survey 123 was introduced as a COVID-19 contact tracing application to digitise the case-based forms and provide real-time results from the laboratories to GHS and other stakeholders. The laboratory backend allowed the testing laboratories access to specific information about each patient (sample) collected by the fieldworkers. The regional supervisors’ backend web application provided accessing test results for confidentiality and timely communication of results.Conclusion: Geospatial platforms were successfully established in Ghana to provide timely results to Regional Health Directors and Government decision-makers. This helped to improve the timeliness of response and contact tracing at the district level

IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells

Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al

Validating the implementation of an indicator reporting policies and laws on free public maternal health-related services in the era of universal health coverage: A multi-country cross-sectional study

Background The concept of universal health coverage (UHC) encompasses both access to essential health services and freedom from financial harm. The World Health Organization’s Maternal Newborn Child and Adolescent Health (MNCAH) Policy Survey collects data on policies that have the potential to reduce maternal morbidity and mortality. The indicator, “Are the following health services provided free of charge at point-of-use in the public sector for women of reproductive age?”, captures the free provision of 13 key categories of maternal health-related services, to measure the success of UHC implementation with respect to maternal health. However, it is unknown whether it provides a valid measure of the provision of free care. Therefore, this study compared free maternal healthcare laws and policies against actual practice in three countries. Methods and findings We conducted a cross-sectional study in four districts/provinces in Argentina, Ghana, and India. We performed desk reviews to identify free care laws and policies at the country level and compared those with reports at the global level. We conducted exit interviews with women aged 15–49 years who used a component service or their accompanying persons, as well as with facility chief financial officers or billing administrators, to determine if wome

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient

Validation of a measure to assess decision-making autonomy in family planning services in three low- and middle-income countries: The Family Planning Autonomous Decision-Making scale (FP-ADM)

Background Integrating measures of respectful care is an important priority in family planning programs, aligned with maternal health efforts. Ensuring women can make autonomous reproductive health decisions is an important indicator of respectful care. While scales have been developed and validated in family planning for dimensions of person-centered care, none focus specifically on decision-making autonomy. The Mothers Autonomy in Decision-Making (MADM) scale measures autonomy in decision-making during maternity care. We adapted the MADM scale to measure autonomy surrounding a woman’s decision to use a contraceptive method within the context of contraceptive counselling. This study presents a psychometric validation of the Family Planning Autonomous Decision-Making (FP-ADM) scale using data from Argentina, Ghana, and India. Methods and findings We used cross-sectional data from women in four subnational areas in Argentina (n = 890), Ghana (n = 1,114), and India (n = 1,130). In each area, 20 primary sampling units (PSUs) were randomly selected based on probability proportional to size. Households were randomly selected in Ghana and India. In Argentina, all facilities providing reproductive and maternal health services within selected PSUs were included and women were randomly selected upon exiting the facility. Interviews were conducted with a sample of 360 women per district. In total, 890 women completed the FP-ADM in Argentina, 1,114 in Ghana and 1,130 in India. To measure autonomous decision-making within FP service delivery, we adapted the items of the MADM scale to focus on family planning. To assess the scale’s psychometric properties, we first examined the eigenvalues and conducted a parallel analysis to determine the number of factors. We then conducted exploratory factor analysis to determine which items to retain. The resulting factors were then identified based on the corresponding items. Internal consistency reliability was assessed with Cronbach’s alpha. We assessed both convergent and divergent construct validity by examining associations with expected outcomes related to the underlying construct. The Eigenvalues and parallel analysis suggested a two-factor solution. The two underlying dimensions of the construct were identified as “Bidirectional Exchange of Information” (Factor 1) and “Empowered Choice” (Factor 2). Cronbach’s alpha was calculated for the full scale and each subscale. Results suggested good internal consistency of the scale. There was a strong, significant positive association between whether a woman expressed satisfaction with quality of care received from the healthcare provider and her FP-ADM score in all three countries and a significant negative association between a woman’s FP-ADM score and her stated desire to switch contraceptive methods in the future. Conclusions Our results suggest the FP-ADM is a valid instrument to assess decision-making autonomy in contraceptive counseling and service delivery in diverse low- and middle-income countries. The scale evidenced strong construct, convergent, and divergent validity and high internal consistency reliability. Use of the FP-ADM scale could contribute to improved measurement of person-centered family planning services

Authorization of midwives to perform basic emergency obstetric and newborn care signal functions in Argentina, Ghana, and India: A multi-country validation study of a key global maternal and newborn health indicator

BACKGROUND: Midwives' authorization to deliver the seven basic emergency obstetric and newborn care (BEmONC) functions is a core policy indicator in global monitoring frameworks, yet little evidence supports whether such data are captured accurately, or whether authorization demonstrates convergence with midwives' skills and actual provision of services. In this study, we aimed to validate the data reported in global monitoring frameworks (criterion validity) and to determine whether a measure of authorization is a valid indicator for BEmONC availability (construct validity). METHODS: We conducted a validation study in Argentina, Ghana, and India. To assess accuracy of the reported data on midwives' authorization to provide BEmONC services, we reviewed national regulatory documents and compared with reported country-specific data in Countdown to 2030 and the World Health Organization Maternal, Newborn, Child and Adolescent Health Policy Survey. To assess whether authorization demonstrates convergent validity with midwives' skills, training, and performance of BEmONC signal functions, we surveyed 1257 midwives/midwifery professionals and assessed variance. RESULTS: We detected discrepancies between data reported in the global monitoring frameworks and the national regulatory framework in all three countries. We found wide variations between midwives' authorization to perform signal functions and their self-reported skills and actual performance within the past 90 days. The percentage of midwives who reported performing all signal functions for which they were authorized per country-specific regulations was 17% in Argentina, 23% in Ghana, and 31% in India. Additionally, midwives in all three countries reported performing some signal functions that the national regulations did not authorize. CONCLUSION: Our findings suggest limitations in criterion and construct validity for this indicator in Argentina, Ghana, and India. Some signal functions such as assisted vaginal delivery may be obsolete based on current practice patterns. Findings suggest the need to re-examine the emergency interventions that should be included as BEmONC signal functions

Poor prognostic clinicopathologic features correlate with VEGF expression but not with PTEN expression in squamous cell carcinoma of the larynx

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess the relationship between expression of vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted in chromosome ten (PTEN), angiogenesis and clinicopathological parameters of squamous cell carcinoma of the larynx.</p> <p>Methods</p> <p>We examined immunohistochemical expression of VEGF and PTEN and CD34 for microvessel density (MVD) in sections of formalin-fixed, paraffin embedded tissue blocks of 140 patients with squamous cell carcinoma of the larynx. The intensity of VEGF and PTEN staining and the proportion of cells staining were scored.</p> <p>Results</p> <p>The tumor grade was not significantly related to PTEN expression, but it was to VEGF expression (p = 0.400; p = 0.015, respectively). While there was no significant relationship between PTEN expression and tumor size and cartilage invasion (p = 0.311, p = 0.128), there was a significant relationship between the severity of VEGF expression and tumor size (p = 0.006) and lymph node metastasis (p = 0.048) but not cartilage invasion (p = 0.129). MVD was significantly higher in high-grade tumors (p = 0.003) but had no significant relationship between MVD, lymph node metastasis, and cartilage invasion (p = 0.815, p = 0.204). There was also no significant relationship between PTEN and VEGF expression (p = 0.161) and between PTEN and VEGF expression and the MVD (p = 0.120 and p = 0.175, respectively).</p> <p>Conclusions</p> <p>Increased VEGF expression may play an important role in the outcome of squamous cell carcinoma of the larynx. PTEN expression was not related to VEGF expression and clinicopathological features of squamous cell carcinoma of the larynx.</p

Validating indicators for monitoring availability and geographic distribution of emergency obstetric and newborn care (EmoNC) facilities: A study triangulating health system, facility, and geospatial data

Availability of emergency obstetric and newborn care (EmONC) is a strong supply side measure of essential health system capacity that is closely and causally linked to maternal mortality reduction and fundamentally to achieving universal health coverage. The World Health Organization’s indicator “Availability of EmONC facilities” was prioritized as a core indicator to prevent maternal death. The indicator focuses on whether there are sufficient emergency care facilities to meet the population need, but not all facilities designated as providing EmONC function as such. This study seeks to validate “Availability of EmONC” by comparing the value of the indicator after accounting for key aspects of facility functionality and an alternative measure of geographic distribution. This study takes place in four subnational geographic areas in Argentina, Ghana, and India using a census of all birthing facilities. Performance of EmONC in the 90 days prior to data collection was assessed by examining facility records. Data were collected on facility operating hours, staffing, and availability of essential medications. Population estimates were generated using ArcGIS software using WorldPop to estimate the total population, and the number of women of reproductive age (WRA), pregnancies and births in the study areas. In addition, we estimated the population within two-hours travel time of an EmONC facility by incorporating data on terrain from Open Street Map. Using these data sources, we calculated and compared the value of the indicator after incorporating data on facility performance and functionality while varying the reference population used. Further, we compared its value to the proportion of the population within two-hours travel time of an EmONC facility. Included in our study were 34 birthing facilities in Argentina, 51 in Ghana, and 282 in India. Facility performance of basic EmONC (BEmONC) and comprehensive EmONC (CEmONC) signal functions varied considerably. One facility (4.8%) in Ghana and no facility in India designated as BEmONC had performed all seven BEmONC signal functions. In Argentina, three (8.8%) CEmONC-designated facilities performed all nine CEmONC signal functions, all located in Buenos Aires Region V. Four CEmONC-designated facilities in Ghana (57.1%) and the three CEmONC-designated facilities in India (23.1%) evidenced full CEmONC performance. No sub-national study area in Argentina or India reached the target of 5 BEmONC-level facilities per 20,000 births after incorporating facility functionality yet 100% did in Argentina and 50% did in India when considering only facility designation. Demographic differences also accounted for important variation in the indicator’s value. In Ghana, the total population in Tolon within 2 hours travel time of a designated EmONC facility was estimated at 99.6%; however, only 91.1% of women of reproductive age were within 2 hours travel time. Comparing the value of the indicator when calculated using different definitions reveals important inconsistencies, resulting in conflicting information about whether the threshold for sufficient coverage is met. This raises important questions related to the indicator’s validity. To provide a valid measure of effective coverage of EmONC, the construct for measurement should extend beyond the most narrow definition of availability and account for functionality and geographic accessibility

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Association of antigen processing machinery and HLA class I defects with clinicopathological outcome in cervical carcinoma

HLA class I loss is a significant mechanism of immune evasion by cervical carcinoma, interfering with the development of immunotherapies and cancer vaccines. We report the systematic investigation of HLA class I and antigen processing machinery component expression and association with clinical outcome. A tissue microarray containing carcinoma lesions from 109 cervical carcinoma patients was stained for HLA class I heavy chains, β2-microglobulin, LMP2, LMP7, LMP10, TAP1, TAP2, ERAP1, tapasin, calreticulin, calnexin and ERp57. A novel staining evaluation method was used to ensure optimal accuracy and reliability of expression data, which were correlated with known clinicopathological parameters. Partial HLA class I loss was significantly associated with decreased 5-years overall survival (61% vs. 83% for normal expression; P < 0.05) and was associated with decreased 5-years disease-free survival (DFS) (65% vs. 82% for normal expression; P = 0.05). All APM components except LMP10, calnexin and calreticulin were down-regulated in a substantial number of cases and, except ERAP1, correlated significantly with HLA class I down-regulation. LMP7, TAP1 and ERAP1 loss was significantly associated with decreased overall and (except LMP7) DFS (P < 0.05 and 0.005, respectively). ERAP1 down-regulation was an independent predictor for worse overall and DFS in multivariate analysis (HR 3.08; P < 0.05 and HR 2.84; P < 0.05, respectively). HLA class I and APM component down-regulation occur frequently in cervical carcinoma, while peptide repertoire alterations due to ERAP1 loss are a major contributing factor to tumour progression and mortality