Outbreak detection algorithms for seasonal disease data: a case study using ross river virus disease

<p>Abstract</p> <p>Background</p> <p>Detection of outbreaks is an important part of disease surveillance. Although many algorithms have been designed for detecting outbreaks, few have been specifically assessed against diseases that have distinct seasonal incidence patterns, such as those caused by vector-borne pathogens.</p> <p>Methods</p> <p>We applied five previously reported outbreak detection algorithms to Ross River virus (RRV) disease data (1991-2007) for the four local government areas (LGAs) of Brisbane, Emerald, Redland and Townsville in Queensland, Australia. The methods used were the Early Aberration Reporting System (EARS) C1, C2 and C3 methods, negative binomial cusum (NBC), historical limits method (HLM), Poisson outbreak detection (POD) method and the purely temporal SaTScan analysis. Seasonally-adjusted variants of the NBC and SaTScan methods were developed. Some of the algorithms were applied using a range of parameter values, resulting in 17 variants of the five algorithms.</p> <p>Results</p> <p>The 9,188 RRV disease notifications that occurred in the four selected regions over the study period showed marked seasonality, which adversely affected the performance of some of the outbreak detection algorithms. Most of the methods examined were able to detect the same major events. The exception was the seasonally-adjusted NBC methods that detected an excess of short signals. The NBC, POD and temporal SaTScan algorithms were the only methods that consistently had high true positive rates and low false positive and false negative rates across the four study areas. The timeliness of outbreak signals generated by each method was also compared but there was no consistency across outbreaks and LGAs.</p> <p>Conclusions</p> <p>This study has highlighted several issues associated with applying outbreak detection algorithms to seasonal disease data. In lieu of a true gold standard, a quantitative comparison is difficult and caution should be taken when interpreting the true positives, false positives, sensitivity and specificity.</p

Live calcium imaging of Aedes aegypti neuronal tissues reveals differential importance of chemosensory systems for life-history-specific foraging strategies.

BackgroundThe mosquito Aedes aegypti has a wide variety of sensory pathways that have supported its success as a species as well as a highly competent vector of numerous debilitating infectious pathogens. Investigations into mosquito sensory systems and their effects on behavior are valuable resources for the advancement of mosquito control strategies. Numerous studies have elucidated key aspects of mosquito sensory systems, however there remains critical gaps within the field. In particular, compared to that of the adult form, there has been a lack of studies directed towards the immature life stages. Additionally, although numerous studies have pinpointed specific sensory receptors as well as responding motor outputs, there has been a lack of studies able to monitor both concurrently.ResultsTo begin filling aforementioned gaps, here we engineered Ae. aegypti to ubiquitously express a genetically encoded calcium indicator, GCaMP6s. Using this strain, combined with advanced microscopy, we simultaneously measured live stimulus-evoked calcium responses in both neuronal and muscle cells with a wide spatial range and resolution.ConclusionsBy coupling in vivo live calcium imaging with behavioral assays we were able to gain functional insights into how stimulus-evoked neural and muscle activities are represented, modulated, and transformed in mosquito larvae enabling us to elucidate mosquito sensorimotor properties important for life-history-specific foraging strategies

'Swimmability' : a key element for communities to safely engage with Australian urban rivers

Australia’s largest cities are growing, and this is placing increasing pressure on urban waterways. There is a growing awareness that the quality of life in Australian urban communities is enhanced through the engagement of people with healthy urban rivers. Swimming, boating, and fishing in many Australian urban waterways are popular recreational activities. Swimming and other activities associated with waterways contributes to quality of life in urban communities. Swimming in urban rivers can be risky. Hazards include dangerous currents, aquatic plants, submerged hazards, algal blooms, and unsuitable water quality. In Sydney, Australia’s largest City, swimming is popular in the Hawkesbury-Nepean River. Data from showed that E. coli levels in the river occasionally exceeded safe recreational guidelines for human health. The results are not reported to the public. We believe that it is more important than ever that government, industry and scientific bodies work to protect and improve the water quality of Australian urban rivers as our cities grow. Sharing this information with the community needs to consider education programs, public forums, and timely communication of the current state of local Australian urban rivers regarding their ‘swimmability’

NOTCH1 inhibition in vivo results in mammary tumor regression and reduced mammary tumorsphere-forming activity in vitro

INTRODUCTION: NOTCH activation has been recently implicated in human breast cancers, associated with a poor prognosis, and tumor-initiating cells are hypothesized to mediate resistance to treatment and disease relapse. To address the role of NOTCH1 in mammary gland development, transformation, and mammary tumor-initiating cell activity, we developed a doxycycline-regulated mouse model of NOTCH1-mediated mammary transformation. METHODS: Mammary gland development was analyzed by using whole-mount analysis and by flow cytometry in nulliparous transgenic mice maintained in the presence/absence of doxycycline (or intracellular NOTCH1). Mammary tumors were examined histologically and immunophenotyped by staining with antibodies followed by flow cytometry. Tumors were transplanted into mammary fat pads under limiting dilution conditions, and tumor-initiating cell frequency was calculated. Mammary tumor cells were also plated in vitro in a tumorsphere assay in the presence/absence of doxycycline. RNA was isolated from mammary tumor cell lines cultured in the presence/absence of doxycycline and used for gene-expression profiling with Affymetrix mouse arrays. NOTCH1-regulated genes were identified and validated by using quantitative real-time polymerase chain reaction (PCR). Mammary tumor-bearing mice were treated with doxycycline to suppress NOTCH1 expression, and disease recurrence was monitored. RESULTS: Similar to published studies, we show that constitutive expression of human intracellular NOTCH1 in the developing mouse mammary gland inhibits side branching and promotes luminal cell fate. These mice develop mammary adenocarcinomas that express cytokeratin (CK) 8/18. In vivo limiting-dilution analyses revealed that these mammary tumors exhibit functional heterogeneity and harbor a rare (1/2,978) mammary tumor-initiating cell population. With this dox-regulated NOTCH1 mammary tumor model, we demonstrate that NOTCH1 inhibition results in mammary tumor regression in vivo and prevents disease recurrence in four of six tumors tested. Consistent with the in vivo data, NOTCH1 inhibition reduces mammary tumorsphere activity in vitro. We also identify the embryonic stem cell transcription factor Nanog as a novel NOTCH1-regulated gene in tumorspheres and in mouse and human breast cancer cell lines. CONCLUSIONS: These data indicate that NOTCH1 inhibition results in mammary tumor regression in vivo and interferes with disease recurrence. We demonstrate that NOTCH1-transformed mouse mammary tumors harbor a rare mammary tumor-initiating population and that NOTCH1 contributes to mammary tumor-initiating activity. This work raises the possibility that NOTCH therapeutics may target mammary tumor-initiating cells in certain human breast cancer subtypes

Multiple Group Membership and Well-Being: Is There Always Strength in Numbers?

A growing body of research points to the value of multiple group memberships for individual well-being. However, much of this work considers group memberships very broadly and in terms of number alone. We conducted two correlational studies exploring how the relationship between multiple group membership and well-being is shaped by (a) the complexity of those groups within the overall self-concept (i.e., social identity complexity: SIC), and (b) the perceived value and visibility of individual group memberships to others (i.e., stigma). Study 1 (N = 112) found a positive relationship between multiple group membership and well-being, but only for individuals high in SIC. This effect was mediated by perceived identity expression and access to social support. Study 2 (N = 104) also found that multiple group memberships indirectly contributed to well-being via perceived identity expression and social support, as well as identity compatibility and perceived social inclusion. But, in this study the relationship between multiple group memberships and well-being outcomes was moderated by the perceived value and visibility of group memberships to others. Specifically, possessing multiple, devalued and visible group memberships compromised well-being relative to multiple valued group memberships, or devalued group memberships that were invisible. Together, these studies suggest that the benefits of multiple group membership depend on factors beyond their number. Specifically, the features of group memberships, individually and in combination, and the way in which these guide self-expression and social action, determine whether these are a benefit or burden for individual well-being

Cold Pressor Pain Response in Children with Cancer

Objective: The goal of this study was to examine pain responses in pediatric patients with cancer. Method: Children (ages 6 to 18) undergoing treatment for cancer (N=68) completed the cold pressor task. Results: Average pain tolerance was 118.22 seconds (SD=101.18) and 40% of the children kept their hand in the water the entire 4-minute ceiling. On a 0 to 10 numeric rating scale, children reported a pain severity of 5.07 (SD=3.47) at their first report of pain, a pain severity of 5.94 (SD=3.54) at their maximum report of pain, and a pain severity of 5.33 (SD=3.72) at the time they reached pain tolerance. Children receiving chemotherapy agents (N=56) with possible neuropathic effects exhibited higher pain tolerance compared with children not receiving such treatments (N=10), β=0.84, SE=0.38, Wald χ21=4.88, P=0.027, hazard ratio=2.33, 95% confidence interval (1.10-4.92). Conclusions: This study provides data on experimental pain responses in a sample of children undergoing cancer treatment and suggests that pain experience may be moderated by cancer treatment type

A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data

Gauging the threat: the first population estimate for white sharks in South Africa using photo identification and automated software

South Africa is reputed to host the world’s largest remaining population of white sharks, yet no studies have accurately determined a population estimate based on mark-recapture of live individuals. We used dorsal fin photographs (fin IDs) to identify white sharks in Gansbaai, South Africa, from January 2007 - December 2011. We used the computer programme DARWIN to catalogue and match fin IDs of individuals; this is the first study to successfully use the software for white shark identification. The programme performed well despite a number of individual fins showing drastic changes in dorsal fin shape over time. Of 1682 fin IDs used, 532 unique individuals were identified. We estimated population size using the open-population POPAN parameterisation in Program MARK, which estimated the superpopulation size at 908 (95% confidence interval 808-1008). This estimated population size is considerably larger than those described at other aggregation areas of the species and is comparable to a previous South African population estimate conducted 16 years prior. Our assessment suggests the species has not made a marked recovery since being nationally protected in 1991. As such, additional international protection may prove vital for the long-term conservation of this threatened species

Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.

The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, progressive neuronal degeneration and massive glial activation. Advances have been made in genetic diagnosis and counseling for families. However, comprehensive treatment programs that delay or halt disease progression have been elusive. Current disease management is primarily targeted at controlling the symptoms rather than curing the disease. Recognizing the growing need for transparency and synergistic efforts to move the field forward, this review will provide an overview of the therapeutic approaches currently being pursued in preclinical and clinical trials to treat different forms of NCL as well as provide insight to novel therapeutic approaches in development for the NCLs