Validation of a prognostic scoring system for locally recurrent nasopharyngeal carcinoma treated by stereotactic radiosurgery

<p>Abstract</p> <p>Background</p> <p>Selection of patients with local failure of nasopharyngeal carcinoma (NPC) for appropriate type of salvage treatment can be difficult due to the lack of data on comparative efficacy of different salvage treatments. The purpose of the present study was to validate a previously published prognostic scoring system for local failures of NPC treated by radiosurgery based on reported results in the literature.</p> <p>Methods</p> <p>A literature search yielded 3 published reports on the use of radiosurgery as salvage treatment of NPC that contained sufficient clinical information for validation of the scoring system. Prognostic scores of 18 patients from these reports were calculated and actuarial survival rates were estimated and compared to the original cohort used to design the prognostic scoring system. The area under the receiver operating characteristic curve was also determined and compared between the current and original patient groups.</p> <p>Results</p> <p>The calculated prognostic scores ranged from 0.32 to 1.21, with 15 patients assigned to the poor prognostic group and 3 to the intermediate prognostic group. The actuarial 3-year survival rates in the intermediate and poor prognostic groups were 67% and 0%, respectively. These results were comparable to the observed 3-year survival rates of 74% and 23% in the intermediate and poor prognostic group in the original reports. The area under the receiver operating characteristic curve for the current patient group was 0.846 which was similar to 0.841 in the original group.</p> <p>Conclusion</p> <p>The previously published prognostic scoring system demonstrated good prediction of treatment outcome after radiosurgery in a small group of NPC patients with poor prognosis. Prospective study to validate the scoring system is currently being carried out in our institution.</p

Differential Developmental Deficits in Retinal Function in the Absence of either Protein Tyrosine Sulfotransferase-1 or -2

To investigate the role(s) of protein-tyrosine sulfation in the retina and to determine the differential role(s) of tyrosylprotein sulfotransferases (TPST) 1 and 2 in vision, retinal function and structure were examined in mice lacking TPST-1 or TPST-2. Despite the normal histologic retinal appearance in both Tpst1−/− and Tpst2−/− mice, retinal function was compromised during early development. However, Tpst1−/− retinas became electrophysiologically normal by postnatal day 90 while Tpst2−/− mice did not functionally normalize with age. Ultrastructurally, the absence of TPST-1 or TPST-2 caused minor reductions in neuronal plexus. These results demonstrate the functional importance of protein-tyrosine sulfation for proper development of the retina and suggest that the different phenotypes resulting from elimination of either TPST-1 or -2 may reflect differential expression patterns or levels of the enzymes. Furthermore, single knock-out mice of either TPST-1 or -2 did not phenocopy mice with double-knockout of both TPSTs, suggesting that the functions of the TPSTs are at least partially redundant, which points to the functional importance of these enzymes in the retina

Optimal Conservation of Migratory Species

Background. Migratory animals comprise a significant portion of biodiversity worldwide with annual investment for their conservation exceeding several billion dollars. Designing effective conservation plans presents enormous challenges. Migratory species are influenced by multiple events across land and sea-regions that are often separated by thousands of kilometres and span international borders. To date, conservation strategies for migratory species fail to take into account how migratory animals are spatially connected between different periods of the annual cycle (i.e. migratory connectivity) bringing into question the utility and efficiency of current conservation efforts. Methodology/Principal Findings. Here, we report the first framework for determining an optimal conservation strategy for a migratory species. Employing a decision theoretic approach using dynamic optimization, we address the problem of how to allocate resources for habitat conservation for a Neotropical-Nearctic migratory bird, the American redstart Setophaga ruticilla, whose winter habitat is under threat. Our first conservation strategy used the acquisition of winter habitat based on land cost, relative bird density, and the rate of habitat loss to maximize the abundance of birds on the wintering grounds. Our second strategy maximized bird abundance across the entire range of the species by adding the constraint of maintaining a minimum percentage of birds within each breeding region in North America using information on migratory connectivity as estimated from stable-hydrogen isotopes in feathers. We show that failure to take into account migratory connectivity may doom some regional populations to extinction, whereas including information on migratory connectivity results in the protection of the species across its entire range. Conclusions/Significance. We demonstrate that conservation strategies for migratory animals depend critically upon two factors: knowledge of migratory connectivity and the correct statement of the conservation problem. Our framework can be used to identify efficient conservation strategies for migratory taxa worldwide, including insects, birds, mammals, and marine organisms

Towards modeling the retailer as a brand: A social construction of the grocery store from the customer standpoint

As a highly customer-sensitive business, retailing is one of the most socially active industries. Nevertheless, when addressing retailers as brands, the retailing literature has failed to account for their unique social orientation, exposing a gap in the literature. This paper utilizes the sociological view of brands to socially construct a conceptual retail brand model from the customer standpoint. An ethnographic study of grocery retailing revealed that the store has, metaphorically, a tree-shaped culture, which can organically model the interplay between building the retailer brand as a culture and the phases constituting the social-self concept

Advanced Genomic Data Mining

As data banks increase their size, one of the current challenges in bioinformatics is to be able to query them in a sensible way. Information is contained in differen

The natural history and management of hamstring injuries

Hamstring injuries in sport can be debilitating. The anatomical complexity of this muscle makes uniform assessment of injury epidemiology difficult and insures that post-injury management strategies must be individually focused. This article reviews the anatomy of the hamstring, its role in athletic movement, common mechanisms of injury, and management guidelines with the goal of return into sporting activity in mind

The effect of a sports chiropractic manual therapy intervention on the prevention of back pain, hamstring and lower limb injuries in semi-elite Australian Rules footballers: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hamstring injuries are the most common injury in Australian Rules football. It was the aims to investigate whether a sports chiropractic manual therapy intervention protocol provided in addition to the current best practice management could prevent the occurrence of and weeks missed due to hamstring and other lower-limb injuries at the semi-elite level of Australian football.</p> <p>Methods</p> <p>Sixty male subjects were assessed for eligibility with 59 meeting entry requirements and randomly allocated to an intervention (n = 29) or control group (n = 30), being matched for age and hamstring injury history. Twenty-eight intervention and 29 control group participants completed the trial. Both groups received the current best practice medical and sports science management, which acted as the control. Additionally, the intervention group received a sports chiropractic intervention. Treatment for the intervention group was individually determined and could involve manipulation/mobilization and/or soft tissue therapies to the spine and extremity. Minimum scheduling was: 1 treatment per week for 6 weeks, 1 treatment per fortnight for 3 months, 1 treatment per month for the remainder of the season (3 months). The main outcome measure was an injury surveillance with a missed match injury definition.</p> <p>Results</p> <p>After 24 matches there was no statistical significant difference between the groups for the incidence of hamstring injury (OR:0.116, 95% CI:0.013-1.019, p = 0.051) and primary non-contact knee injury (OR:0.116, 95% CI:0.013-1.019, p = 0.051). The difference for primary lower-limb muscle strains was significant (OR:0.097, 95%CI:0.011-0.839, p = 0.025). There was no significant difference for weeks missed due to hamstring injury (4 v14, χ2:1.12, p = 0.29) and lower-limb muscle strains (4 v 21, χ2:2.66, p = 0.10). A significant difference in weeks missed due to non-contact knee injury was noted (1 v 24, χ2:6.70, p = 0.01).</p> <p>Conclusions</p> <p>This study demonstrated a trend towards lower limb injury prevention with a significant reduction in primary lower limb muscle strains and weeks missed due to non-contact knee injuries through the addition of a sports chiropractic intervention to the current best practice management.</p> <p>Trial registration</p> <p>The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12608000533392).</p

Missense mutation of Brain Derived Neurotrophic Factor (BDNF) alters neurocognitive performance in patients with mild traumatic brain injury: a longitudinal study

The predictability of neurocognitive outcomes in patients with traumatic brain injury is not straightforward. The extent and nature of recovery in patients with mild traumatic brain injury (mTBI) are usually heterogeneous and not substantially explained by the commonly known demographic and injury-related prognostic factors despite having sustained similar injuries or injury severity. Hence, this study evaluated the effects and association of the Brain Derived Neurotrophic Factor (BDNF) missense mutations in relation to neurocognitive performance among patients with mTBI. 48 patients with mTBI were prospectively recruited and MRI scans of the brain were performed within an average 10.1 (SD 4.2) hours post trauma with assessment of their neuropsychological performance post full Glasgow Coma Scale (GCS) recovery. Neurocognitive assessments were repeated again at 6 months follow-up. The paired t-test, Cohen’s d effect size and repeated measure ANOVA were performed to delineate statistically significant differences between the groups [wildtype G allele (Val homozygotes) vs. minor A allele (Met carriers)] and their neuropsychological performance across the time point (T1 = baseline/ admission vs. T2 = 6th month follow-up). Minor A allele carriers in this study generally performed more poorly on neuropsychological testing in comparison wildtype G allele group at both time points. Significant mean differences were observed among the wildtype group in the domains of memory (M = -11.44, SD = 10.0, p = .01, d = 1.22), executive function (M = -11.56, SD = 11.7, p = .02, d = 1.05) and overall performance (M = -6.89 SD = 5.3, p = .00, d = 1.39), while the minor A allele carriers showed significant mean differences in the domains of attention (M = -11.0, SD = 13.1, p = .00, d = .86) and overall cognitive performance (M = -5.25, SD = 8.1, p = .01, d = .66).The minor A allele carriers in comparison to the wildtype G allele group, showed considerably lower scores at admission and remained impaired in most domains across the timepoints, although delayed signs of recovery were noted to be significant in the domains attention and overall cognition. In conclusion, the current study has demonstrated the role of the BDNF rs6265 Val66Met polymorphism in influencing specific neurocognitive outcomes in patients with mTBI. Findings were more detrimentally profound among Met allele carriers

Junín Virus Infection of Human Hematopoietic Progenitors Impairs In Vitro Proplatelet Formation and Platelet Release via a Bystander Effect Involving Type I IFN Signaling

Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VHF), AHF patients present with fever and hemorrhagic complications. Although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts have been described. Thrombocytopenia is a common feature in VHF syndromes, and it is a major sign for its diagnosis. However, the underlying pathogenic mechanism has not yet been elucidated. We hypothesized that thrombocytopenia results from a viral-triggered alteration of the megakaryo/thrombopoiesis process. Therefore, we evaluated the impact of JUNV on megakaryopoiesis using an in vitro model of human CD34+ cells stimulated with thrombopoietin. Our results showed that CD34+ cells are infected with JUNV in a restricted fashion. Infection was transferrin receptor 1 (TfR1)-dependent and the surface expression of TfR1 was higher in infected cultures, suggesting a novel arenaviral dissemination strategy in hematopoietic progenitor cells. Although proliferation, survival, and commitment in JUNV-infected cultures were normal, viral infection impaired thrombopoiesis by decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN α/β) was implicated as a key paracrine mediator. Among the relevant molecules studied, only the transcription factor NF-E2 showed a moderate decrease in expression in megakaryocytes from either infected cultures or after type I IFN treatment. Moreover, type I IFN-treated megakaryocytes presented ultrastructural abnormalities resembling the reported thrombocytopenic NF-E2−/− mouse phenotype. Our study introduces a potential mechanism for thrombocytopenia in VHF and other diseases associated with increased bone marrow type I IFN levels

Competition and habitat quality influence age and sex distribution in wintering rusty blackbirds.

Bird habitat quality is often inferred from species abundance measures during the breeding and non-breeding season and used for conservation management decisions. However, during the non-breeding season age and sex classes often occupy different habitats which suggest a need for more habitat-specific data. Rusty Blackbird (Euphagus carolinus) is a forested wetland specialist wintering in bottomland hardwood forests in the south-eastern U. S. and belongs to the most steeply declining songbirds in the U.S. Little information is available to support priority birds such as the Rusty Blackbird wintering in this threatened habitat. We assessed age and sex distribution and body condition of Rusty Blackbirds among the three major habitats used by this species in the Lower Mississippi Alluvial Valley and also measured food availability. Overall, pecan groves had the highest biomass mainly driven by the amount of nuts. Invertebrate biomass was highest in forests but contributed only a small percentage to overall biomass. Age and sex classes were unevenly distributed among habitats with adult males primarily occupying pecan groves containing the highest nut biomass, females being found in forests which had the lowest nut biomass and young males primarily staying in forest fragments along creeks which had intermediate nut biomass. Males were in better body condition than females and were in slightly better condition in pecan groves. The results suggest that adult males occupy the highest quality habitat and may competitively exclude the other age and sex classes