To evaluate the impact of cisplatin cumulative dose (CDDP-D) and smoking pack-years (PYs) on cause-specific survival (CSS) and overall survival (OS) in human papillomavirus–positive (HPV+) ...oropharyngeal carcinoma (OPSCC) using the eighth edition tumour-node-metastasis (TNM) staging classification (TNM8).
We reviewed patients with HPV+ OPSCC treated with high-dose CDDP and intensity-modulated radiotherapy between 2005 and 2015 at Princess Margaret Cancer Centre. CSS and OS were compared according to CDDP-D <200/=200/>200 mg/m2 stratified by TNM8.
A total of 482 consecutive patients were evaluated (stage I/II/III: N = 189/174/119; CDDP-D <200/=200/>200 mg/m2: N = 112/220/150). Median follow-up duration was 5.1 years (range: 0.6–12.8). Five-year CSS and OS differed by stages I/II/III: 96%/85%/88% (p=0.005) and 93%/84%/78% (p = 0.001), respectively. Five-year CSS by CDDP-D <200/=200/>200 mg/m2 was similar in stage I (98%/95%/95%, p = 0.74) and stage II (88%/84%/84%, p = 0.86) but different in stage III (76%/98%/84%, p = 0.02). Five-year OS by CDDP-D <200/=200/>200 mg/m2 did not differ significantly among stages. In the multivariable analysis, CDDP-D <200 mg/m2 did not influence CSS in the whole cohort versus = 200/>200 mg/m2 (p=0.53/0.79, respectively) but was associated with reduced CSS in stage III subgroup versus =200 mg/m2 (=200 mg/m2 versus < 200 mg/m2 hazard ratio HR = 0.08; 95% confidence interval CI: 0.01–0.67; p = 0.02). Higher smoking PYs had no effect on CSS (p = 0.34) but reduced OS in the whole cohort (HR = 1.14 95% CI: 1.02–1.27, p=0.01).
CDDP-D correlated with neither survival nor disease-specific outcomes in this large and homogeneous HPV+ cohort, although reduced CSS was observed in stageIII HPV+ OPSCC receiving CDDP-D <200 mg/m2. Smoking PYs were negatively associated with OS but not with CSS.
•Cisplatin cumulative dose has no impact on outcome in human papillomavirus–positive (HPV+) oropharyngeal cancers.•Higher smoking pack-years affect overall survival but not cancer-specific survival.•There was reduced survival in patients with stage III disease with total cisplatin dose <200 mg/m2.•The 8th edition tumour-node-metastasis (TNM) stage grouping separates well survival in HPV+ disease.•Chemoradiotherapy should remain the standard of care while awaiting prospective data.
Early and robust T cell responses have been associated with survival from Lassa fever (LF), but the Lassa virus-specific memory responses have not been well characterized. Regions within the virus ...surface glycoprotein (GPC) and nucleoprotein (NP) are the main targets of the Lassa virus-specific T cell responses, but, to date, only a few T cell epitopes within these proteins have been identified. We identified GPC and NP regions containing T cell epitopes and HLA haplotypes from LF survivors and used predictive HLA-binding algorithms to identify putative epitopes, which were then experimentally tested using autologous survivor samples. We identified 12 CD8-positive (CD8
) T cell epitopes, including epitopes common to both Nigerian and Sierra Leonean survivors. These data should be useful for the identification of dominant Lassa virus-specific T cell responses in Lassa fever survivors and vaccinated individuals as well as for designing vaccines that elicit cell-mediated immunity.
The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.
The behavioral ecology of Sonoran Desert Tortoises (Gopherus morafkai) remains relatively unstudied. In general, Sonoran Desert Tortoises (SDTs) differentially use incised washes and rocky slopes and ...avoid open flats and intermountain valleys, except during apparent emigration events. We know relatively little about the temporal pattern of space use in SDTs and even less about such use in relation to sex. We observed activity of adult and juvenile SDTs via radiotelemetry, and hatchling activity incidentally, over a 3-yr period in central Arizona. The SDTs were most active in the fall (August–October) but exhibited a second peak of activity in the spring (April). On average, males moved longer distances than did females in every month of the year when SDTs were active. Distance moved by females in the fall was significantly greater than all other months except April; a similar pattern of greater male movement in the fall was apparent but not statistically significant. Activity of adults was detected in virtually every month of the year except January; at least one hatchling was observed active in every month of the year. We conclude that adult SDTs home range areas 1) are consistent in size and placement across multiple years and, for females especially, may include a “migratory” pattern to north slopes following summer rains, where they encounter a higher diversity and abundance of food plants; 2) are highly overlapping in females but less so in males; and 3) contain a few refuges in relatively lower elevation washes that are used consistently, especially during the hot, dry summer (May and June), and that are selected over many other available caliche refuges.
Sonoran Desert habitat in southern Arizona is increasingly altered by urban development near metropolitan areas. Understanding how reptiles respond in these impacted habitats is critical to ...conservation efforts to retain intact biotic communities, especially those with a high diversity of reptile species. We surveyed snakes at one impacted site on the northern edge of the Phoenix metropolitan area in desert/urban interface, and at another site in a desert/rural interface near Florence, Arizona. The site near Phoenix was lower in species richness (15 spp.), and evenness: two snake species accounted for 75 % of all snakes encountered (total = 420). The site near Florence was higher in species richness (19 spp.), and a more even community: no species accounted for more than 20 % of snakes encountered (total = 594). Sampling methodology had a strong influence on species richness and abundance of snakes at the respective sites: road riding, coverboards, and traps each provided evidence of unique species missed by other methods. These results were compared with inventories at three other sites in the central Sonoran Desert of Arizona, and are consistent with the view that the impacted site near Phoenix is uneven, potentially as a result of a single species reacting to shifts in prey availability.
A retrospective review.
The aim of this study was to assess correction of pelvic obliquity in children with cerebral palsy (CP) scoliosis postoperatively and 5 years after posterior spinal fusion ...with pelvic fixation using unit rods, sacral-alar-iliac (SAI) screws, or iliac screws.
There are multiple options for pelvic fixation in children with scoliosis secondary to CP. The long-term differences in outcomes between these fixation methods are still unclear.
A multicenter review identified records of 70 children with CP who underwent posterior spinal fusion for scoliosis using unit rods (n = 9), SAI screws (n = 19), or iliac screws (n = 42). Patients younger than 18 years with 5-year follow-up were included. Pelvic obliquity and major coronal curve measurements were compared using preoperative, (first erect) postoperative, and 5-year follow-up radiographs. Implant-related complications were noted. Alpha = 0.05.
For all groups, there was a significant difference between preoperative and postoperative pelvic obliquity that was maintained at 5 years. At 5-year follow-up, pelvic obliquity was significantly higher in the IS group (12°) compared with the unit rod group (4°, P = 0.001) and SAI screw group (6°) (P = 0.006). Implant-related complications were as follows: unit rod group, one patient (reoperation); SAI screw group, none; iliac screw group, six patients, including three cases of loss of connection between the rod and the iliac screw, two prominent screws, and one loose screw.
Correction of pelvic obliquity for children with CP-related scoliosis was achieved postoperatively using unit rods, SAI screws, and iliac screws. Implant-related complications and reoperations were most common in the iliac screw group. At 5-year follow-up, the iliac screw group had loss of major curve correction and less correction of pelvic obliquity than the unit rod and SAI screw groups.
3.
Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and ...significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.
The ecological consequences of impoundment construction on riparian systems throughout the U.S. Southwest has profoundly affected a variety of organisms, including many amphibians. To better ...understand the current extent of hybridization and changes in genetic composition over time in Bufo (Anaxyrus) woodhousii and Bufo microscaphus, we used microsatellite loci to evaluate 260 individuals representing 10 total populations constituting B. woodhousii, B. microscaphus, and putative hybrids along the Agua Fria River in Arizona during two time periods (1992–97 and 2009–10). Consistent with prior work with these two anurans documenting unidirectional replacement or genetic introgression, we predicted that microsatellites would provide evidence of directional introgression of B. woodhousii into B. microscaphus. The putative hybrid populations exhibited the highest number of alleles, and B. microscaphus exhibited the lowest number of alleles. Structure analysis indicated K = 2 as the best-fit population number for both time periods. All pairwise F-statistics were highly significant, corroborating differentiation among populations as inferred by structure analysis. The principal coordinates analysis demonstrated three distinct clusters of individuals that corresponded strongly with prior morphological and mitochondrial assignments within this region over both sampling periods. Our findings indicate that the genetic identity of B. microscaphus remains distinct from B. woodhousii and the hybrids, suggesting that the genetic structure of the corresponding populations has remained intact. Bufo woodhousii has not replaced B. microscaphus along the Agua Fria River beyond those habitats directly associated with impoundment construction.
Urbanization is rapidly enveloping isolated remnants of Sonoran Desert habitat in southern Arizona. Understanding the means by which herpetofauna can persist in these habitats in the face of multiple ...impacts is vital to conservation efforts to retain intact biotic communities, especially those with a high diversity of reptile species. We surveyed ten preserves in the Phoenix Metropolitan region for Desert (Phrynosoma platyrhinos) and Regal (Phrynosoma solare) horned lizards, members of an iconic group of lizards of the Southwest. At least one horned lizard species is found in preserves across the range in size, age and habitat axes we assessed, provided that their primary prey, seed-harvester ants (Pogonomyrmex rugosus) are present. Horned lizards are apparently absent from one large preserve where they were once present, perhaps as a result of a decline in seed-harvester ants, but they may have been absent from other preserves due to the lack of appropriate habitat for their prey rather than due to direct anthropogenic impacts.
Little is known regarding the activity of desert tortoises during winter, especially for the Sonoran Desert Tortoise (Gopherus morafkai). We observed adult, juvenile, and hatchling G. morafkai active ...during November, December, January, and February at 3 field sites in upland Sonoran Desert in central Arizona. At 1 site all individuals under observation (n = 36), including males, females, and hatchlings, emerged from hibernacula to drink during the first heavy (> 20 mm) rainfall event (December); at all 3 sites, females were observed active (basking, foraging) during winter much more frequently than were males.
The Arizona Toad (Bufo = Anaxyrus microscaphus) occupied the entire Agua Fria River drainage in central Arizona until relatively recently. By the 1980s, a close relative, Woodhouse's Toad (Bufo ...woodhousii), colonized the lower reaches of the Agua Fria and replaced B. microscaphus at some sites. We tested the hypothesis that habitat disturbance drives replacement of B. microscaphus by B. woodhousii, via hybridization, by examining shifts in the distribution of these toads following the expansion of the Waddell Dam on the lower Agua Fria River in the early 1990s. As of 2010, the high elevation headwaters of the Agua Fria River were still occupied by B. microscaphus, the lower reaches near the confluence with the Gila River were occupied by B. woodhousii, and along the middle reaches, hybridization between these two anurans occurred at the same three sites as documented in the early 1990s. Contrary to expectations, evidence of hybridization along middle reaches of the river is largely unchanged: B. microscaphus has not been replaced by B. woodhousii at any additional sites nor is there any evidence of introgression of woodhousii mtDNA into putatively “pure” microscaphus populations upstream of hybrid sites.
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