Climate Variability and Ross River Virus Transmission in Townsville Region, Australia 1985 to 1996

Background How climate variability affects the transmission of infectious diseases at a regional level remains unclear. In this paper, we assessed the impact of climate variation on the Ross River virus (RRv) transmission in the Townsville region, Queensland, north-east Australia. Methods Population-based information was obtained on monthly variations in RRv cases, climatic factors, sea level, and population growth between 1985 and 1996. Cross-correlations were computed for a series of associations between climate variables (rainfall, maximum temperature, minimum temperature, relative humidity and high tide) and the monthly incidence of RRv disease over a range of time lags. The impact of climate variability on RRv transmission was assessed using the seasonal auto-regressive integrated moving average (SARIMA) model. Results There were significant correlations of the monthly incidence of RRv to rainfall, maximum temperature, minimum temperature and relative humidity, all at a lag of 2 months, and high tide in the current month. The results of SARIMA models show that monthly average rainfall (β=0.0012, p=0.04) and high tide (β=0.0262, p=0.01) were significantly associated with RRv transmission, although temperature and relative humidity did not seem to have played an important role in the Townsville region. Conclusions Rainfall, and high tide were likely to be key determinants of RRv transmission in the Townsville region

Clinically relevant safety issues associated with St. John's wort product labels

<p>Abstract</p> <p>Background</p> <p>St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA.</p> <p>Methods</p> <p>Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.</p> <p>Results</p> <p>Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of <it>a priori </it>safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.</p> <p>Conclusion</p> <p>The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.</p

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Photonic quantum technologies

The first quantum technology, which harnesses uniquely quantum mechanical effects for its core operation, has arrived in the form of commercially available quantum key distribution systems that achieve enhanced security by encoding information in photons such that information gained by an eavesdropper can be detected. Anticipated future quantum technologies include large-scale secure networks, enhanced measurement and lithography, and quantum information processors, promising exponentially greater computation power for particular tasks. Photonics is destined for a central role in such technologies owing to the need for high-speed transmission and the outstanding low-noise properties of photons. These technologies may use single photons or quantum states of bright laser beams, or both, and will undoubtably apply and drive state-of-the-art developments in photonics

Design of cohort studies in chronic diseases using routinely collected databases when a prescription is used as surrogate outcome

BACKGROUND: There has been little research on design of studies based on routinely collected data when the clinical endpoint of interest is not recorded, but can be inferred from a prescription. This often happens when exploring the effect of a drug on chronic diseases. Using the LifeLink claims database in studying the possible anti-inflammatory effects of statins in rheumatoid arthritis (RA), oral steroids (OS) were treated as surrogate of inflammatory flare-ups. We compared two cohort study designs, the first using time to event outcomes and the second using quantitative amount of the surrogate. METHODS: RA patients were extracted from the LifeLink database. In the first study, patients were split into two sub-cohorts based on whether they were using OS within a specified time window of the RA index date (first record of RA). Using Cox models we evaluated the association between time-varying exposure to statins and (i) initiation of OS therapy in the non-users of OS at RA index date and (ii) cessation of OS therapy in the users of OS at RA index date. In the second study, we matched new statin users to non users on age and sex. Zero inflated negative binomial models were used to contrast the number of days' prescriptions of OS in the year following date of statin initiation for the two exposure groups. RESULTS: In the unmatched study, the statin exposure hazard ratio (HR) of initiating OS in the 31451 non-users of OS at RA index date was 0.96(95% CI 0.9,1.1) and the statin exposure HR of cessation of OS therapy in the 6026 users of OS therapy at RA index date was 0.95 (0.87,1.05). In the matched cohort of 6288 RA patients the statin exposure rate ratio for duration on OS therapy was 0.88(0.76,1.02). There was digit preference for outcomes in multiples of 7 and 30 days. CONCLUSIONS: The 'time to event' study design was preferable because it better exploits information on all available patients and provides a degree of robustness toward confounding. We found no convincing evidence that statins reduce inflammation in RA patients

Automated Analysis of Craniofacial Morphology Using Magnetic Resonance Images

Quantitative analysis of craniofacial morphology is of interest to scholars working in a wide variety of disciplines, such as anthropology, developmental biology, and medicine. T1-weighted (anatomical) magnetic resonance images (MRI) provide excellent contrast between soft tissues. Given its three-dimensional nature, MRI represents an ideal imaging modality for the analysis of craniofacial structure in living individuals. Here we describe how T1-weighted MR images, acquired to examine brain anatomy, can also be used to analyze facial features. Using a sample of typically developing adolescents from the Saguenay Youth Study (N = 597; 292 male, 305 female, ages: 12 to 18 years), we quantified inter-individual variations in craniofacial structure in two ways. First, we adapted existing nonlinear registration-based morphological techniques to generate iteratively a group-wise population average of craniofacial features. The nonlinear transformations were used to map the craniofacial structure of each individual to the population average. Using voxel-wise measures of expansion and contraction, we then examined the effects of sex and age on inter-individual variations in facial features. Second, we employed a landmark-based approach to quantify variations in face surfaces. This approach involves: (a) placing 56 landmarks (forehead, nose, lips, jaw-line, cheekbones, and eyes) on a surface representation of the MRI-based group average; (b) warping the landmarks to the individual faces using the inverse nonlinear transformation estimated for each person; and (3) using a principal components analysis (PCA) of the warped landmarks to identify facial features (i.e. clusters of landmarks) that vary in our sample in a correlated fashion. As with the voxel-wise analysis of the deformation fields, we examined the effects of sex and age on the PCA-derived spatial relationships between facial features. Both methods demonstrated significant sexual dimorphism in craniofacial structure in areas such as the chin, mandible, lips, and nose

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Laser oscillation in a strongly coupled single quantum dot-nanocavity system

Strong coupling of photons and materials in semiconductor nanocavity systems has been investigated because of its potentials in quantum information processing and related applications, and has been testbeds for cavity quantum electrodynamics (QED). Interesting phenomena such as coherent exchange of a single quantum between a single quantum dot and an optical cavity, called vacuum Rabi oscillation, and highly efficient cavity QED lasers have been reported thus far. The coexistence of vacuum Rabi oscillation and laser oscillation appears to be contradictory in nature, because the fragile reversible process may not survive in laser oscillation. However, recently, it has been theoretically predicted that the strong-coupling effect could be sustained in laser oscillation in properly designed semiconductor systems. Nevertheless, the experimental realization of this phenomenon has remained difficult since the first demonstration of the strong-coupling, because an extremely high cavity quality factor and strong light-matter coupling are both required for this purpose. Here, we demonstrate the onset of laser oscillation in the strong-coupling regime in a single quantum dot (SQD)-cavity system. A high-quality semiconductor optical nanocavity and strong SQD-field coupling enabled to the onset of lasing while maintaining the fragile coherent exchange of quanta between the SQD and the cavity. In addition to the interesting physical features, this device is seen as a prototype of an ultimate solid state light source with an SQD gain, which operates at ultra-low power, with expected applications in future nanophotonic integrated systems and monolithic quantum information devices.Comment: 12 pages, 4 figure