Update on pathology laboratory development and research in advancing regional cancer care in Malawi

The pathology laboratory at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi was established in 2011. We published our initial experiences in laboratory development and telepathology in 2013 and 2016, respectively. The purpose of this paper is to provide an update on our work by highlighting the positive role laboratory development has played in improving regional cancer care and research. In addition, we provide a summary of the adult pathology data from specimens received between July 1, 2011, and May 31, 2019, with an emphasis on malignant diagnoses. We compare these summaries to estimates of cancer incidence in this region to identify gaps and future needs

Brecciation at the grain scale within the lithologies of the Winchcombe Mighei‐like carbonaceous chondrite

The Mighei‐like carbonaceous (CM) chondrites have been altered to various extents by water–rock reactions on their parent asteroid(s). This aqueous processing has destroyed much of the primary mineralogy of these meteorites, and the degree of alteration is highly heterogeneous at both the macroscale and nanoscale. Many CM meteorites are also heavily brecciated juxtaposing clasts with different alteration histories. Here we present results from the fine‐grained team consortium study of the Winchcombe meteorite, a recent CM chondrite fall that is a breccia and contains eight discrete lithologies that span a range of petrologic subtypes (CM2.0–2.6) that are suspended in a cataclastic matrix. Coordinated multitechnique, multiscale analyses of this breccia reveal substantial heterogeneity in the extent of alteration, even in highly aqueously processed lithologies. Some lithologies exhibit the full range and can comprise nearly unaltered coarse‐grained primary components that are found directly alongside other coarse‐grained components that have experienced complete pseudomorphic replacement by secondary minerals. The preservation of the complete alteration sequence and pseudomorph textures showing tochilinite–cronstedtite intergrowths are replacing carbonates suggest that CMs may be initially more carbonate rich than previously thought. This heterogeneity in aqueous alteration extent is likely due to a combination of microscale variability in permeability and water/rock ratio generating local microenvironments as has been established previously. Nevertheless, some of the disequilibrium mineral assemblages observed, such as hydrous minerals juxtaposed with surviving phases that are typically more fluid susceptible, can only be reconciled by multiple generations of alteration, disruption, and reaccretion of the CM parent body at the grain scale

Brecciation at the grain scale within the lithologies of the Winchcombe Mighei-like carbonaceous chondrite

The Mighei‐like carbonaceous (CM) chondrites have been altered to various extents by water–rock reactions on their parent asteroid(s). This aqueous processing has destroyed much of the primary mineralogy of these meteorites, and the degree of alteration is highly heterogeneous at both the macroscale and nanoscale. Many CM meteorites are also heavily brecciated juxtaposing clasts with different alteration histories. Here we present results from the fine‐grained team consortium study of the Winchcombe meteorite, a recent CM chondrite fall that is a breccia and contains eight discrete lithologies that span a range of petrologic subtypes (CM2.0–2.6) that are suspended in a cataclastic matrix. Coordinated multitechnique, multiscale analyses of this breccia reveal substantial heterogeneity in the extent of alteration, even in highly aqueously processed lithologies. Some lithologies exhibit the full range and can comprise nearly unaltered coarse‐grained primary components that are found directly alongside other coarse‐grained components that have experienced complete pseudomorphic replacement by secondary minerals. The preservation of the complete alteration sequence and pseudomorph textures showing tochilinite–cronstedtite intergrowths are replacing carbonates suggest that CMs may be initially more carbonate rich than previously thought. This heterogeneity in aqueous alteration extent is likely due to a combination of microscale variability in permeability and water/rock ratio generating local microenvironments as has been established previously. Nevertheless, some of the disequilibrium mineral assemblages observed, such as hydrous minerals juxtaposed with surviving phases that are typically more fluid susceptible, can only be reconciled by multiple generations of alteration, disruption, and reaccretion of the CM parent body at the grain scale

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Multiple benzene-formation paths in a fuel-rich cyclohexane flame

Li W, Law ME, Westmoreland PR, Kasper T, Hansen N, Kohse-Höinghaus K. Multiple benzene-formation paths in a fuel-rich cyclohexane flame. COMBUSTION AND FLAME. 2011;158(11):2077-2089

Benzene formation in a stoichiometric cyclohexane flame

Law ME, Westmoreland PR, Cool TA, et al. Benzene formation in a stoichiometric cyclohexane flame. In: PROCEEDINGS OF THE 4TH JOINT MEETING OF THE US SECTIONS OF THE COMBUSTION INSTITUTE. 2005

FIGURE 4 from The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma <i>In Vivo</i> Models Confers a Major Survival Advantage in a CD24-dependent Manner

Evaluation of the Zika viral time course on neuroblastoma tumors by IHC. ZIKV-treated tumors were compared with vehicle-treated tumors at each timepoint. A, IMR-32 tumors were H&E stained at day 0, 2, 5, and 7 posttreatment. Percent necrosis is indicated under each image. B, IMR-32 tumors were stained using a Zika viral NS1 protein antibody at day 0, 2, 5, and 7 posttreatment. C, SK-N-AS tumors were H&E stained at day 0, 4, 7, and 10 posttreatment. Percent necrosis is indicated under each image. D, SK-N-AS tumors were stained using a Zika viral NS1 protein antibody at day 0, 4, 7, and 10 posttreatment. Tissues were stained using a Leica Bond Maxfive and images were generated using an Olympus BX43 at 40x magnification with a 10x zoom.</p

Supplementary Figure 3 from The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma <i>In Vivo</i> Models Confers a Major Survival Advantage in a CD24-dependent Manner

Effect of the Zika viral treatment of neuroblastoma tumors on tumor mass over time.</p

FIGURE 3 from The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma <i>In Vivo</i> Models Confers a Major Survival Advantage in a CD24-dependent Manner

Time course of the In vivo modeling of the Zika viral treatment of neuroblastoma tumors. ZIKV was introduced once at a concentration of 2 × 106 pfu for all tumors in NCr nude mice. A, Time course assessment of the application of ZIKV to IMR-32 tumors. Tumor size was measured at day 0, 2, 5, and 7 posttreatment compared with vehicle control treatment. Each timepoint within the study utilized an n = 3 for both vehicle- and Zika-treated cohorts. Error bars represent SD. *, P t test, days 2, 5, and 7. B, Viral copy number was also measured in vehicle control treated mice for each timepoint in the IMR-32 tumor model, measuring the tumor, kidneys, spleen, liver, heart, and brain by absolute quantification PCR. C, Time course assessment of the application of ZIKV to SK-N-AS tumors. Tumor size was measured at day 0, 4, 7, and 10 posttreatment compared with vehicle control treatment. Each timepoint within the study utilized an n = 3 for both vehicle- and Zika-treated cohorts. Error bars represent SD. *, P t test, days 4, 7, and 10. D, Viral copy number was also measured in vehicle control treated mice for each timepoint in SK-N-AS tumor models, measuring the tumor, kidneys, spleen, liver, heart, and brain by absolute quantification PCR. E, Relative expression for CD24 was assessed using qRT-PCR at each timepoint for IMR-32 tumors. F, Relative expression for CD24 was assessed using qRT-PCR at each timepoint for SK-N-AS tumors. Both qRT-PCR studies compare cells with tumors for each neuroblastoma. Expression was normalized to GAPDH. All qPCR data shown are the composite of triplicate wells acquired from triplicate experiments. Error bars represent SD. *, P In vitro cells, one-way ANOVA for tumor day 0, 4, 7, and10.</p

Supplementary Figure 5 from The Oncolytic Activity of Zika Viral Therapy in Human Neuroblastoma <i>In Vivo</i> Models Confers a Major Survival Advantage in a CD24-dependent Manner

Effect on the change in tumor mass of Zika viral treated CD24-Exogenously expressing SK-N-AS tumors.</p