Challenges of consolidating evidence collected during a pandemic and lessons for the future.

OBJECTIVE: To illustrate the challenges encountered when gathering rapidly synthesized evidence in response to the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this article, we describe the challenges encountered when we performed a systematic literature review (SLR) of randomized controlled trials (RCTs) on the efficacy and safety of treatments for severe COVID-19. The methods of the SLR are described in full, to show the context of our objectives. Then we use the results of the SLR to demonstrate the problems of producing synthesized evidence in this setting. RESULTS: Various challenges were identified during this SLR. These were primarily a result of heterogeneity in the study methodology of eligible studies. Definitions of the patient populations and outcome measurements were highly variable and the majority of studies demonstrated a high risk of bias, preventing quantitative synthesis of the collated evidence. CONCLUSION: Consolidating evidence from RCTs evaluating COVID-19 interventions was problematic. Guidance is needed for scenarios with high rapid output in primary research.

The causal nexus between imports and economic growth in China, India and G7 countries: granger causality analysis in the frequency domain.

This research examine the causal nexus between imports and economic growth in China, India and G7 economies. We use BC granger causality analysis in the frequency domain short (temporary) and long term (permanent) causality. Our results suggested that, there is a frequency domain (high and low) proof of the bi-directional causal nexus between imports and economic growth. The imports and economic growth in most economies seem to be long-term and short-term dependent. This empirical study shows that policymakers of these big economies need to analyze the transformation in the import-economic growth causality robustness throughout the year when planning policy actions.

Indirect effects of COVID-19 pandemic on reproductive, maternal, newborn and child health services in Pakistan.

Background: COVID-19 is having many impacts on health, economy and social life; some due to the indirect effects of closure of health facilities to curb the spread. Closures were implemented in Pakistan from March 2020, affecting provision of reproductive, maternal, newborn and child health (RMNCH) services. Aims: To appraise the effects of containment and lockdown policies on RMNCH service utilization in order to develop an early response to avoid the catastrophic impact of COVID-19 on RMNCH in Pakistan. Methods: Routine monitoring data were analysed for indicators utilization of RMNCH care. The analysis was based on Period 1 (January-May 2020, first wave of COVID-19); Period 2 (June-September 2020, declining number of cases of COVID-19); and Period 3 (October-December 2020, second wave of COVID-19). We also compared data from May and December 2020 with corresponding months in 2019, to ascertain whether changes were due to COVID-19. Results: Reduced utilization was noted for all RMNCH indicators during Periods 1 and 3. There was a greater decline in service utilization during the first wave, and the highest reduction (~82%) was among children aged < 5 years, who were treated for pneumonia. The number of caesarean sections dropped by 57%, followed by institutional deliveries and first postnatal visit (37% each). Service utilization increased from June to September, but the second wave of COVID-19 led to another decrease. Conclusion: To reinstate routine services, priority actions and key areas include continued provision of family planning services along with uninterrupted immunization campaigns and routine maternal and child services.

Novel Chlamydiae and Amoebophilus endosymbionts are prevalent in wild isolates of the model social amoeba Dictyostelium discoideum.

Amoebae interact with bacteria in multifaceted ways. Amoeba predation can serve as a selective pressure for the development of bacterial virulence traits. Bacteria may also adapt to life inside amoebae, resulting in symbiotic relationships. Indeed, particular lineages of obligate bacterial endosymbionts have been found in different amoebae. Here, we screened an extensive collection of Dictyostelium discoideum wild isolates for the presence of these bacterial symbionts using endosymbiont specific PCR primers. We find that these symbionts are surprisingly common, identified in 42% of screened isolates (N = 730). Members of the Chlamydiae phylum are particularly prevalent, occurring in 27% of the amoeba isolated. They are novel and phylogenetically distinct from other Chlamydiae. We also found Amoebophilus symbionts in 8% of screened isolates (N = 730). Antibiotic-cured amoebae behave similarly to their Chlamydiae or Amoebophilus-infected counterparts, suggesting that these endosymbionts do not significantly impact host fitness, at least in the laboratory. We found several natural isolates were co-infected with multiple endosymbionts, with no obvious fitness effect of co-infection under laboratory conditions. The high prevalence and novelty of amoeba endosymbiont clades in the model organism D. discoideum opens the door to future research on the significance and mechanisms of amoeba-symbiont interactions.

Prevention of Mother-to-child HIV Transmission in Nigeria: Six Years' Experience from a Tertiary Institution.

BACKGROUND: In line with global standards and progress made in Prevention of Motherto- Child Transmission (PMTCT), an assessment of the outcome of Early Infant Diagnosis in northern Nigeria is necessary to evaluate progress towards zero Human immunodeficiency Virus (HIV) infection among children. OBJECTIVES: This study assessed the infection rate and risk factors for mother-to-child HIV transmission among HIV-exposed children in Kano, northwest Nigeria. METHODS: Using a retrospective cohort design, pregnant HIV-positive women and their exposed infants were recruited over a period of six years (2010 to 2016). Participants were enrolled during pregnancy or at delivery in the PMTCT clinic of a tertiary health facility in Kano, Nigeria. The main outcomes for the study were Early infant diagnosis positivity for HIV at 6 weeks and risk factors for positivity. RESULTS: Of the 1,514 infants studied, early infant diagnosis was positive for HIV among 13 infants (0.86%). Infants whose mothers did not have antiretroviral therapy (adjusted Prevalence Ratio aPR = 2.58, 95%CI (1.85- 3.57)), who had mixed feeding (aPR = 12.06, 95%CI (9.86- 14.70)), and those not on antiretroviral prophylaxis (aPR = 20.39, 95%CI (16.04- 25.71)) were more likely to be infected with HIV. HIV-exposed infants on nevirapine and zidovudine prophylaxis were 95% and 74%, respectively, less likely to be infected with HIV. CONCLUSION: HIV infection rate remains high among HIV-exposed infants whose mothers did not receive PMTCT services. Scaling up proven interventions of early commencement of antiretroviral treatment for mothers, adherence to antiretroviral prophylaxis, and avoidance of mixed feeding among HIV-exposed infants would protect future generations from HIV infection.

Non-invasive classification of non-small cell lung cancer: a comparison between random forest models utilising radiomic and semantic features.

OBJECTIVE: Non-invasive distinction between squamous cell carcinoma and adenocarcinoma subtypes of non-small-cell lung cancer (NSCLC) may be beneficial to patients unfit for invasive diagnostic procedures or when tissue is insufficient for diagnosis. The purpose of our study was to compare the performance of random forest algorithms utilizing CT radiomics and/or semantic features in classifying NSCLC. METHODS: Two thoracic radiologists scored 11 semantic features on CT scans of 106 patients with NSCLC. A set of 115 radiomics features was extracted from the CT scans. Random forest models were developed from semantic (RM-sem), radiomics (RM-rad), and all features combined (RM-all). External validation of models was performed using an independent test data set (n = 100) of CT scans. Model performance was measured with out-of-bag error and area under curve (AUC), and compared using receiver-operating characteristics curve analysis on the test data set. RESULTS: The median (interquartile-range) error rates of the models were: RF-sem 24.5 % (22.6 - 37.5 %), RF-rad 35.8 % (34.9 - 38.7 %), and RM-all 37.7 % (37.7 - 37.7). On training data, both RF-rad and RF-all gave perfect discrimination (AUC = 1), which was significantly higher than that achieved by RF-sem (AUC = 0.78; p < 0.0001). On test data, however, RM-sem model (AUC = 0.82) out-performed RM-rad and RM-all (AUC = 0.5 and AUC = 0.56; p < 0.0001), neither of which was significantly different from random guess ( p = 0.9 and 0.6 respectively). CONCLUSION: Non-invasive classification of NSCLC can be done accurately using random forest classification models based on well-known CT-derived descriptive features. However, radiomics-based classification models performed poorly in this scenario when tested on independent data and should be used with caution, due to their possible lack of generalizability to new data. ADVANCES IN KNOWLEDGE: Our study describes novel CT-derived random forest models based on radiologist-interpretation of CT scans (semantic features) that can assist NSCLC classification when histopathology is equivocal or when histopathological sampling is not possible. It also shows that random forest models based on semantic features may be more useful than those built from computational radiomic features.

Measurement of 18F-FDG PET tumor heterogeneity improves early assessment of response to bevacizumab compared with the standard size and uptake metrics in a colorectal cancer model.

PURPOSE: Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab. MATERIALS AND METHODS: Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent F-FDG PET/CT. Calliper-measured tumor growth (Δvol) and final tumor volume (Volcal), F-FDG PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection. RESULTS: Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (P=0.9), Volcal (P=0.7), Volmet (P=0.28), Metmax (P=0.7), or Metmean (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001). CONCLUSION: F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.

Impact of Ga-68-PSMA PET/CT on management in prostate cancer patients with very early biochemical recurrence after radical prostatectomy.

PURPOSE: With the availability of ultra-sensitive PSA assays, early biochemical relapse (eBCR) of prostate cancer is increasingly being detected at values much lower than the conventional threshold of 0.2 ng/ml. Accurate localisation of disease in this setting may allow treatment modification and improved outcomes, especially in patients with pelvis-confined or extra-pelvic oligometastasis (defined as up to three pelvic nodal or distant sites). We aimed to measure the detection rate of [68]Ga-PSMA-HBNED-CC (PSMA)-PET/CT and its influence on patient management in eBCR of prostate cancer following radical prostatectomy (RP). METHODS: We retrospectively identified 28 patients who underwent PSMA-PET/CT for post-RP eBCR (PSA < 0.5 ng/ml) at our tertiary care cancer centre. Two nuclear medicine physicians independently recorded the sites of PSMA-PET/CT positivity. Multidisciplinary meeting records were accessed to determine changes in management decisions following PSMA-PET/CT scans. RESULTS: The mean age of patients was 65.6 years (range: 50-76.2 years); median PSA was 0.22 ng/ml (interquartile range: 0.15 ng/ml to 0.34 ng/ml). Thirteen patients (46.4%) had received radiotherapy in the past. PSMA-PET/CT was positive in 17 patients (60.7%). Only one patient had polymetastasis (> 3 sites); the remainder either had prostatectomy bed recurrence (n = 2), pelvic oligometastasis (n = 10), or extra-pelvic oligometastasis (n = 4). PSMA-PET/CT resulted in management change in 12 patients (42.8%), involving stereotactic body radiotherapy (n = 6), salvage radiotherapy (n = 4), and systemic treatment (n = 2). CONCLUSIONS: Our findings show that PSMA-PET/CT has a high detection rate in the eBCR setting following RP, with a large proportion of patients found to have fewer than three lesions. PSMA-PET/CT may be of value in patients with early PSA failure, and impact on the choice of potentially curative salvage treatments.

The specificity of Burkholderia symbionts in the social amoeba farming symbiosis: Prevalence, species, genetic and phenotypic diversity.

The establishment of symbioses between eukaryotic hosts and bacterial symbionts in nature is a dynamic process. The formation of such relationships depends on the life history of both partners. Bacterial symbionts of amoebae may have unique evolutionary trajectories to the symbiont lifestyle, because bacteria are typically ingested as prey. To persist after ingestion, bacteria must first survive phagocytosis. In the social amoeba Dictyostelium discoideum, certain strains of Burkholderia bacteria are able to resist amoebal digestion and maintain a persistent relationship that includes carriage throughout the amoeba's social cycle that culminates in spore formation. Some Burkholderia strains allow their host to carry other bacteria, as food. This carried food is released in new environments in a trait called farming. To better understand the diversity and prevalence of Burkholderia symbionts and the traits they impart to their amoebae hosts, we first screened 700 natural isolates of D. discoideum and found 25% infected with Burkholderia. We next used a multilocus phylogenetic analysis and identified two independent transitions by Burkholderia to the symbiotic lifestyle. Finally, we tested the ability of 38 strains of Burkholderia from D. discoideum, as well as strains isolated from other sources, for traits relevant to symbiosis in D. discoideum. Only D. discoideum native isolates belonging to the Burkholderia agricolaris, B. hayleyella, and B. bonniea species were able to form persistent symbiotic associations with D. discoideum. The Burkholderia-Dictyostelium relationship provides a promising arena for further studies of the pathway to symbiosis in a unique system.

Diversity of Free-Living Environmental Bacteria and Their Interactions With a Bactivorous Amoeba.

A small subset of bacteria in soil interact directly with eukaryotes. Which ones do so can reveal what is important to a eukaryote and how eukaryote defenses might be breached. Soil amoebae are simple eukaryotic organisms and as such could be particularly good for understanding how eukaryote microbiomes originate and are maintained. One such amoeba, Dictyostelium discoideum, has both permanent and temporary associations with bacteria. Here we focus on culturable bacterial associates in order to interrogate their relationship with D. discoideum. To do this, we isolated over 250 D. discoideum fruiting body samples from soil and deer feces at Mountain Lake Biological Station. In one-third of the wild D. discoideum we tested, one to six bacterial species were found per fruiting body sorus (spore mass) for a total of 174 bacterial isolates. The remaining two-thirds of D. discoideum fruiting body samples did not contain culturable bacteria, as is thought to be the norm. A majority (71.4%) of the unique bacterial haplotypes are in Proteobacteria. The rest are in either Actinobacteria, Bacteriodetes, or Firmicutes. The highest bacterial diversity was found in D. discoideum fruiting bodies originating from deer feces (27 OTUs), greater than either of those originating in shallow (11 OTUs) or in deep soil (4 OTUs). Rarefaction curves and the Chao1 estimator for species richness indicated the diversity in any substrate was not fully sampled, but for soil it came close. A majority of the D. discoideum-associated bacteria were edible by D. discoideum and supported its growth (75.2% for feces and 81.8% for soil habitats). However, we found several bacteria genera were able to evade phagocytosis and persist in D. discoideum cells through one or more social cycles. This study focuses not on the entire D. discoideum microbiome, but on the culturable subset of bacteria that have important eukaryote interactions as prey, symbionts, or pathogens. These eukaryote and bacteria interactions may provide fertile ground for investigations of bacteria using amoebas to gain an initial foothold in eukaryotes and of the origins of symbiosis and simple microbiomes.

Investigating the histopathologic correlates of 18F-FDG PET heterogeneity in non-small-cell lung cancer.

PURPOSE: Despite the growing use of fluorine-18-fluorodeoxyglucose (F-FDG) PET texture analysis to measure intratumoural heterogeneity in cancer research, the biologic basis of F-FDG PET-derived texture variables is poorly understood. We aimed to assess correlations between F-FDG PET-derived texture variables and whole-slide image (WSI)-derived metrics of tumour cellularity and spatial heterogeneity. PATIENTS AND METHODS: Twenty-two patients with non-small-cell lung cancer prospectively underwent F-FDG PET imaging before tumour resection. We tested nine F-FDG PET parameters: metabolically active tumour volume, total lesion glycolysis, mean standardized uptake value (SUVmean), first-order entropy, energy, skewness, kurtosis, grey-level co-occurrence matrix entropy and lacunarity (SUV-lacunarity). From the haematoxylin and eosin-stained WSIs, we derived mean tumour-cell density (MCD) and lacunarity (path-lacunarity). Spearman's correlation analysis and agglomerative hierarchical clustering were performed to assess variable associations. RESULTS: Tumour volumes ranged from 2.2 to 74 cm (median: 17.9 cm). MCD correlated positively with total lesion glycolysis (rs: 0.46, P: 0.007) and SUVmean (rs : 0.55; P: 0.008) and negatively with skewness and kurtosis (rs: -0.47 for both; P: 0.028 and 0.026, respectively). SUV-lacunarity and path-lacunarity were positively correlated (rs: 0.5; P: 0.018). On cluster analysis, larger tumours trended towards higher SUVmean and entropy with a predominance of tightly concentrated high SUV-voxels (negative skewness and low kurtosis on the histogram); on WSI analysis such larger tumours also displayed generally higher MCD and low SUV-lacunarity and path-lacunarity. CONCLUSION: Our data suggest that histopathological MCD and lacunarity are associated with several commonly used F-FDG PET-derived indices including SUV-lacunarity, metabolically active tumour volume, SUVmean, entropy, skewness, and kurtosis, and thus may explain the biological basis of F-FDG PET-uptake heterogeneity in non-small-cell lung cancer.

The impact of rural residence and HIV infection on poor tuberculosis treatment outcomes in a large urban hospital: a retrospective cohort analysis.

BACKGROUND: Successful tuberculosis (TB) treatment is essential to effective TB control. TB-HIV coinfection, social determinants and access to services influenced by rural residence can affect treatment outcome. We examined the separate and joint effects of rural residence and HIV infection on poor treatment outcome among patients enrolled in a large TB treatment centre in Kano, Nigeria. METHODS: We retrospectively analysed a cohort of patients with TB enrolled in a large urban TB clinic in northern Nigeria, from January 2010 to December 2014. Poor treatment outcome was defined as death, default or treatment failure. We used Poisson regression to model rates and determine the relative risks (and 95% confidence intervals, CI) of poor treatment outcomes. RESULTS: Among 1381 patients included in the analysis, 28.4% were rural residents; 39.8% were HIV-positive; and 46.1% had a poor treatment outcome. Approximately 65 and 38% of rural and urban residents, respectively, had a poor treatment outcome. Rural residents had 2.74 times (95% CI: 2.27-3.29) the risk of having a poor treatment outcome compared to urban residents. HIV-positive patients had 1.4 times (95% CI: 1.16-1.69) the risk of poor treatment outcome compared to HIV-negative patients. The proportion of poor treatment outcome attributable to rural residence (population attributable fraction, PAF) was 25.6%. The PAF for HIV infection was 11.9%. The effect of rural residence on poor treatment outcome among HIV-negative patients (aRR:4.07; 95%CI:3.15-5.25) was more than twice that among HIV-positive patients (aRR:1.99; 95%CI:1.49-2.64). CONCLUSION: Rural residents attending a large Nigerian TB clinic are at increased risk of having poor treatment outcomes, and this risk is amplified among those that are HIV-negative. Our findings indicate that rural coverage of HIV services may be better than TB services. These findings highlight the importance of expanding coverage of TB services to ensure prompt diagnosis and commencement of treatment, especially among rural-dwellers in resource-limited settings.

The effects of segmentation algorithms on the measurement of 18F-FDG PET texture parameters in non-small cell lung cancer.

BACKGROUND: Measures of tumour heterogeneity derived from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans are increasingly reported as potential biomarkers of non-small cell lung cancer (NSCLC) for classification and prognostication. Several segmentation algorithms have been used to delineate tumours, but their effects on the reproducibility and predictive and prognostic capability of derived parameters have not been evaluated. The purpose of our study was to retrospectively compare various segmentation algorithms in terms of inter-observer reproducibility and prognostic capability of texture parameters derived from non-small cell lung cancer (NSCLC) 18F-FDG PET/CT images. Fifty three NSCLC patients (mean age 65.8 years; 31 males) underwent pre-chemoradiotherapy 18F-FDG PET/CT scans. Three readers segmented tumours using freehand (FH), 40% of maximum intensity threshold (40P), and fuzzy locally adaptive Bayesian (FLAB) algorithms. Intraclass correlation coefficient (ICC) was used to measure the inter-observer variability of the texture features derived by the three segmentation algorithms. Univariate cox regression was used on 12 commonly reported texture features to predict overall survival (OS) for each segmentation algorithm. Model quality was compared across segmentation algorithms using Akaike information criterion (AIC). RESULTS: 40P was the most reproducible algorithm (median ICC 0.9; interquartile range [IQR] 0.85-0.92) compared with FLAB (median ICC 0.83; IQR 0.77-0.86) and FH (median ICC 0.77; IQR 0.7-0.85). On univariate cox regression analysis, 40P found 2 out of 12 variables, i.e. first-order entropy and grey-level co-occurence matrix (GLCM) entropy, to be significantly associated with OS; FH and FLAB found 1, i.e., first-order entropy. For each tested variable, survival models for all three segmentation algorithms were of similar quality, exhibiting comparable AIC values with overlapping 95% CIs. CONCLUSIONS: Compared with both FLAB and FH, segmentation with 40P yields superior inter-observer reproducibility of texture features. Survival models generated by all three segmentation algorithms are of at least equivalent utility. Our findings suggest that a segmentation algorithm using a 40% of maximum threshold is acceptable for texture analysis of 18F-FDG PET in NSCLC.

Going to scale: design and implementation challenges of a program to increase access to skilled birth attendants in Nigeria.

BACKGROUND: The lack of availability of skilled providers in low- and middle- income countries is considered to be an important barrier to achieving reductions in maternal and child mortality. However, there is limited research on programs increasing the availability of skilled birth attendants in developing countries. We study the implementation of the Nigeria Midwives Service Scheme, a government program that recruited and deployed nearly 2,500 midwives to rural primary health care facilities across Nigeria in 2010. An outcome evaluation carried out by this team found only a modest impact on the use of antenatal care and no measurable impact on skilled birth attendance. This paper draws on perspectives of policymakers, program midwives, and community residents to understand why the program failed to have the desired impact. METHODS: We conducted semi-structured interviews with federal, state and local government policy makers and with MSS midwives. We also conducted focus groups with community stakeholders including community leaders and male and female residents. RESULTS: Our data reveal a range of design, implementation and operational challenges ranging from insufficient buy-in by key stakeholders at state and local levels, to irregular and in some cases total non-provision of agreed midwife benefits that likely contributed to the program's lack of impact. These challenges not only created a deep sense of dissatisfaction with the program but also had practical impacts on service delivery likely affecting households' uptake of services. CONCLUSION: This paper highlights the challenge of effectively scaling up maternal and child health interventions. Our findings emphasize the critical importance of program design, particularly when programs are implemented at scale; the need to identify and involve key stakeholders during planning and implementation; the importance of clearly defining lines of authority and responsibility that align with existing structures; and the necessity for multi-faceted interventions that address multiple barriers at the same time.

Magnetic Resonance (MR) Imaging of Vascular Malformations.

Vascular malformations pose a diagnostic and therapeutic challenge due to the broad differential diagnosis as well as common utilization of inadequate or inaccurate classification systems among healthcare providers. Therapeutic approaches to these lesions vary based on the type, size, and extent of the vascular anomaly, necessitating accurate diagnosis and classification. Magnetic resonance (MR) imaging (MRI) is an effective modality for classifying vascular anomalies due to its ability to delineate the extent and anatomic relationship of the malformation to adjacent structures. In addition to anatomical mapping, the complete evaluation of vascular anomalies includes hemodynamic characterization. Dynamic time-resolved contrast-enhanced MR angiography provides information regarding hemodynamics of vascular anomalies, differentiating high- and low-flow vascular malformations. Radiologists must identify the MRI features of vascular malformations for better diagnosis and classification.

The effect of increasing the supply of skilled health providers on pregnancy and birth outcomes: evidence from the midwives service scheme in Nigeria.

BACKGROUND: Limited availability of skilled health providers in developing countries is thought to be an important barrier to achieving maternal and child health-related MDG goals. Little is known, however, about the extent to which scaling-up supply of health providers will lead to improved pregnancy and birth outcomes. We study the effects of the Midwives Service Scheme (MSS), a public sector program in Nigeria that increased the supply of skilled midwives in rural communities on pregnancy and birth outcomes. METHODS: We surveyed 7,104 women with a birth within the preceding five years across 12 states in Nigeria and compared changes in birth outcomes in MSS communities to changes in non-MSS communities over the same period. RESULTS: The main measured effect of the scheme was a 7.3-percentage point increase in antenatal care use in program clinics and a 5-percentage point increase in overall use of antenatal care, both within the first year of the program. We found no statistically significant effect of the scheme on skilled birth attendance or on maternal delivery complications. CONCLUSION: This study highlights the complexity of improving maternal and child health outcomes in developing countries, and shows that scaling up supply of midwives may not be sufficient on its own.

Persistent barriers to care; a qualitative study to understand women's experiences in areas served by the midwives service scheme in Nigeria.

BACKGROUND: The Nigerian Midwives Service Scheme (MSS) is an ambitious human resources project created in 2009 to address supply side barriers to accessing care. Key features include the recruitment and deployment of newly qualified, unemployed and retired midwives to rural primary healthcare centres (PHCs) to ensure improved access to skilled care. This study aimed to understand, from multiple perspectives, the views and experiences of childbearing women living in areas where it has been implemented. METHODS: A qualitative study was undertaken as part of an impact evaluation of the MSS in three states from three geo-political regions of Nigeria. Semi-structured interviews were conducted around nine MSS PHCs with women who had given birth in the past six months, midwives working in the PHCs and policy makers. Focus group discussions were held with wider community members. Coding and analysis of the data was performed in NVivo10 based on the constant comparative approach. RESULTS: The majority of participants reported that there had been positive improvements in maternity care as a result of an increasing number of midwives. However, despite improvements in the perceived quality of care and an apparent willingness to give birth in a PHC, more women gave birth at home than intended. There were some notable differences between states, with a majority of women in one northern state favouring home birth, which midwives and community members commented stemmed from low levels of awareness. The principle reason cited by women for home birth was the sudden onset of labour. Financial barriers, the lack of essential drugs and equipment, lack of transportation and the absence of staff, particularly at night, were also identified as barriers to accessing care. CONCLUSIONS: Our research highlights a number of barriers to accessing care exist, which are likely to have limited the potential for the MSS to have an impact. It suggests that in addition to scaling up the workforce through the MSS, efforts are also needed to address the determinants of care seeking. For the MSS this means that the while the supply side, through the provision of skilled attendance, still needs to be strengthened, this should not be in isolation of addressing demand-side factors.

Imaging Heterogeneity in Lung Cancer: Techniques, Applications, and Challenges.

OBJECTIVE: Texture analysis involves the mathematic processing of medical images to derive sets of numeric quantities that measure heterogeneity. Studies on lung cancer have shown that texture analysis may have a role in characterizing tumors and predicting patient outcome. This article outlines the mathematic basis of and the most recent literature on texture analysis in lung cancer imaging. We also describe the challenges facing the clinical implementation of texture analysis. CONCLUSION: Texture analysis of lung cancer images has been applied successfully to FDG PET and CT scans. Different texture parameters have been shown to be predictive of the nature of disease and of patient outcome. In general, it appears that more heterogeneous tumors on imaging tend to be more aggressive and to be associated with poorer outcomes and that tumor heterogeneity on imaging decreases with treatment. Despite these promising results, there is a large variation in the reported data and strengths of association.

Positron Emission Tomography/Magnetic Resonance Imaging of Gastrointestinal Cancers.

As an integrated system, hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) is able to provide simultaneously complementary high-resolution anatomic, molecular, and functional information, allowing comprehensive cancer phenotyping in a single imaging examination. In addition to an improved patient experience by combining 2 separate imaging examinations and streamlining the patient pathway, the superior soft tissue contrast resolution of MRI and the ability to acquire multiparametric MRI data is advantageous over computed tomography. For gastrointestinal cancers, this would improve tumor staging, assessment of neoadjuvant response, and of the likelihood of a complete (R0) resection in comparison with positron emission tomography or computed tomography.

Burkholderia bacteria infectiously induce the proto-farming symbiosis of Dictyostelium amoebae and food bacteria.

Symbiotic associations can allow an organism to acquire novel traits by accessing the genetic repertoire of its partner. In the Dictyostelium discoideum farming symbiosis, certain amoebas (termed "farmers") stably associate with bacterial partners. Farmers can suffer a reproductive cost but also gain beneficial capabilities, such as carriage of bacterial food (proto-farming) and defense against competitors. Farming status previously has been attributed to amoeba genotype, but the role of bacterial partners in its induction has not been examined. Here, we explore the role of bacterial associates in the initiation, maintenance, and phenotypic effects of the farming symbiosis. We demonstrate that two clades of farmer-associated Burkholderia isolates colonize D. discoideum nonfarmers and infectiously endow them with farmer-like characteristics, indicating that Burkholderia symbionts are a major driver of the farming phenomenon. Under food-rich conditions, Burkholderia-colonized amoebas produce fewer spores than uncolonized counterparts, with the severity of this reduction being dependent on the Burkholderia colonizer. However, the induction of food carriage by Burkholderia colonization may be considered a conditionally adaptive trait because it can confer an advantage to the amoeba host when grown in food-limiting conditions. We observed Burkholderia inside and outside colonized D. discoideum spores after fruiting body formation; this observation, together with the ability of Burkholderia to colonize new amoebas, suggests a mixed mode of symbiont transmission. These results change our understanding of the D. discoideum farming symbiosis by establishing that the bacterial partner, Burkholderia, is an important causative agent of the farming phenomenon.