Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus. Primary infection usually results in varicella (chickenpox), after which VZV becomes latent in ganglionic neurons along the entire neuraxis. As VZV-specific cell-mediated immunity declines in elderly and immunocompromised individuals, VZV reactivates and causes herpes zoster (shingles), frequently complicated by postherpetic neuralgia. VZV reactivation also produces multiple serious neurological and ocular diseases, such as cranial nerve palsies, meningoencephalitis, myelopathy, and VZV vasculopathy, including giant cell arteritis, with or without associated rash. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. Updates on the physical state of VZV DNA and viral gene expression in latently infected ganglia, neuronal, and primate models to study varicella pathogenesis and immunity are presented along with innovations in the immunization of elderly individuals to prevent VZV reactivation. Since the risk of zoster increases with age and since the population that is at least 65 years old is expected to increase to 72 million in 2030, zoster and its attendant serious neurological complications will continue to be a significant health-care burden.Varicella zoster virus (VZV) is an exclusively human alphaherpesvirus. Primary infection causes varicella (chickenpox), after which the virus becomes latent in neurons of cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia along the entire neuraxis. In elderly and immunocompromised individuals, a decline in VZV-specific cell-mediated immunity results in VZV reactivation, typically manifesting as herpes zoster (shingles) in a dermatomal distribution. The annual medical care cost of treating approximately one million cases of zoster in the US is estimated at $1.1 billion, most of which is used to treat immunocompetent adults who are at least 50 years oldZoster is often complicated by chronic pain . VZV reactivation can also produce cranial nerve palsies, meningoencephalitis, VZV vasculopathy, myelopathy, and ocular disease with or without associated rash. Recently, the spectrum of VZV vasculopathy has expanded to include giant cell arteritis (GCA), which is the most common systemic vasculitis in the elderly and which frequently results in vision loss. Herein, we review the clinical, laboratory, imaging, and pathological features of neurological complications of VZV reactivation as well as diagnostic tests to verify VZV infection of the nervous system. We also discuss VZV latency, neuronal and primate models to study varicella pathogenesis and immunity, and immunization of elderly individuals to prevent VZV reactivation.2. Since VZV is latent in ganglia along the entire neuraxis, zoster can develop anywhere on the body. Risk factors for the development of zoster include advanced age3 and immunosuppression, such as in individuals with AIDS or cancer, organ transplant recipients, and individuals who received immunosuppressive medications4. Zoster in an otherwise healthy young person may be the first manifestation of HIV infection5; zoster in children or adolescents is also seen in individuals who acquired primary VZV infectionin utero or in the first year of life; these people are 20.9 times more likely to develop zoster before age 206.Most cases of VZV reactivation manifest as zoster . Rash and pain usually occur within hours to days of each other, although pain may precede rash by weeks to monthsSince VZV is latent in all cranial nerve ganglia and in autonomic (ciliary and otic) ganglia in the head, multiple cranial nerve palsies can develop after zoster. Ophthalmoplegia from involvement of cranial nerve 3, 4, or 6 or any combination thereof is a well-documented complication. Another is weakness or paralysis of facial muscles on one side of the face, associated with vesicles in the ipsilateral external auditory canal (zoster oticus), or on the tympanic membrane, the ipsilateral anterior two thirds of the tongue, or hard palate. The combination of peripheral facial palsy and zoster oticus constitutes the Ramsay Hunt syndrome (RHS). Because the facial nerve is adjacent to the eighth cranial nerve in the facial canal, patients with RHS often have tinnitus, hearing loss, nausea, vomiting, vertigo, or nystagmus. Cranial neuropathies usually occur days to weeks after zoster. The temporal relationship most likely reflects the time needed for the virus to spread transaxonally along trigeminal and other ganglionic afferent fibers, thereafter replicating in small arteries with resultant micro-infarction of cranial nerves (as occurs in patients with diabetes) in the same manner that produces VZV vasculopathy in larger arteries. Importantly, cranial neuropathies produced by VZV can occur in the absence of rash, virologically verified by the detection of VZV DNA or anti-VZV IgG antibody in cerebrospinal fluid (CSF).7. Demyelination may be seen in areas with mononuclear cell (MNC) infiltration and microglial proliferation. In acutely infected ganglia, intranuclear inclusions, viral antigen, and herpesvirus particles are present. Oral antiviral drugs speed healing of zoster rash and shorten the duration of acute pain. Immunocompromised patients and patients with ophthalmic-distribution zoster should receive intravenous acyclovir (10 to 15 mg/kg three times daily for 5 to 7 days).Zoster paresis is characterized by weakness in the arm or diaphragm after cervical distribution zoster or in the leg after lumbar or sacral distribution zoster. Thoracic zoster has been associated with abdominal muscle weakness and hernia. Pathological features of zoster include inflammation and hemorrhagic necrosis with associated neuritis, localized leptomeningitis, unilateral segmental poliomyelitis, and degeneration of related motor and sensory roots8. A possible explanation is that chronic inflammation reflects prolonged viral infection, a notion supported by the detection of VZV DNA in blood MNCs of many patients with PHN (presumably by MNCs trafficking through ganglia productively infected with VZV) and from the favorable response of some patients with PHN to antiviral treatment9. Symptomatic treatment for PHN is challenging. Tricyclic antidepressants, gabapentin, and pregabalin are used as first-line therapies. Many patients with PHN also require topical capsaicin cream, lidocaine patches, capsaicin 8% patches, tramadol, or opioids or a combination of these to help alleviate debilitating pain. Nerve blocks and ablation, as well as nerve stimulators, have variable effectiveness. The potential role of antiviral medications as a treatment for PHN awaits analyses in larger clinical studies.Postherpetic neuralgia (PHN) is defined as pain persisting for more than 3 months after zoster. Age is the single most important predictor, and more than 40% of zoster patients who are more than 60 years old develop PHN. Pathological analysis of ganglia from an early case of PHN of 2.5 months’ duration revealed diffuse and focal infiltration by chronic inflammatory cells, a finding confirmed by the detection of prominent collections of lymphocytes in ganglia from a patient with PHN of 2 years’ duration10. Early diagnosis and aggressive treatment with intravenous acyclovir are beneficial, even in immunocompromised patients11; VZV myelitis may recur, even in immunocompetent patients10. Aside from myelitis, VZV can produce spinal cord infarction from occlusion of spinal arteries12.VZV meningitis, meningoencephalitis, meningoradiculitis, cerebellitis, myelopathy, and vasculopathy may develop after zoster. Importantly, all may develop in the absence of rash, as confirmed by the detection of VZV DNA or anti-VZV antibody (or both) in CSF. VZV myelitis commonly presents as frank invasion of the spinal cord by the virus. Disease is usually progressive and infrequently fatal. Magnetic resonance imaging reveals longitudinal serpiginous-enhancing lesions13, and that antiviral therapy may reduce stroke risk. Retrospective analysis of 30 subjects with VZV vasculopathy, confirmed virologically, revealed that 63% had associated rash, 67% had a CSF pleocytosis, 97% had abnormalities on brain imaging, and 70% had abnormalities on angiographic studies14. Of the 30 subjects, 50% had both large and small artery involvement, 37% had exclusively small artery involvement, and 13% had exclusively large artery involvement. Because 93% of the subjects had intrathecal synthesis of anti-VZV antibodies and only 30% had VZV DNA in CSF, the detection of anti-VZV IgG antibody is the best test for diagnosis consistent with a prior study15. Importantly, since there was no zoster rash in one third of subjects, VZV DNA is absent in 70% of CSF, and there is a 4.2-month delay from onset of rash to neurological disease, thus the diagnosis of VZV vasculopathy is often missed.VZV vasculopathy occurs following productive infection of cerebral arteries and pathological vascular remodeling. The most common manifestations are ischemic stroke, but hemorrhagic stroke, aneurysm, with and without subarachnoid and intracerebral hemorrhage, dolichoectasia, dissection, and venous sinus thrombosis may also be produced by VZV. Although the exact incidence of VZV vasculopathy is unknown, epidemiological studies from Taiwan, Denmark, and the UK have all revealed that the risk of stroke is increased after zoster, particularly when zoster is in the ophthalmic distribution of the trigeminal nerve16. Examination of the inflammatory infiltrate in VZV-infected arteries reveals CD4 and CD8 T cells, macrophages, and rare B cells predominantly located in the adventitia and to a lesser extent in the thickened intima17. In early VZV vasculopathy, neutrophils are present in the adventitia; no neutrophils were detected in late VZV. Consistent with studies of pathological remodeling in coronary and pulmonary arteries, the thickened intima was associated with inflammation in the underlying adventitia, supporting the notion that inflammatory cells secrete soluble factors that contribute to vascular remodeling. A recent study also revealed that VZV-infected brain vascular adventitial fibroblasts produce elevated levels of matrix metalloproteinases that degrade extracellular matrix and may contribute to migration of cells to the lumen and thrombosis as well as to aneurysm formation and hemorrhage18.The proposed mechanism for VZV vasculopathy involved virus reactivation from cranial nerve ganglia followed by transaxonal spread of the virus to the outermost adventitial layer of cerebral arteries whereupon productive virus infection induces pathological vascular remodeling through a direct effect or an indirect effect of virus-induced inflammation. Immunohistochemical studies of VZV-infected cerebral and temporal arteries from patients with VZV vasculopathy show that arteries contain a thickened intima composed of myofibroblasts, loss of medial smooth muscle cells, and a disrupted/duplicated internal elastic lamina19. VZV antigen was present mostly in adventitia, followed by the media and intima  biopsies and normal TA biopsies from subjects who are more than 50 years of age for the presence and distribution of VZV antigen. VZV antigen was found in 61 out of 82 (74%) GCA-positive TAs compared with 1 out of 13 (8%) normal TAs, and most GCA-positive TAs contained viral antigen in skip areas intima . Hematox20. VZV antigen was detected in 45 out of 70 (64%) GCA-negative TAs compared with 11 out of 49 (22%) normal TAs, and extension of our earlier study revealed VZV antigen in 68 out of 93 (73%) GCA-positive TAs compared with 11 out of 49 (22%) normal TAs. VZV antigen was more likely to be present in adventitia of both GCA-negative TAs and GCA-positive TAs than in normal TA adventitia. In GCA-negative subjects whose TAs contained VZV antigen, adventitial inflammation was seen in 36% adjacent to viral antigen but not in any normal TAs. Overall, the prevalence of VZV in TAs of subjects with clinically suspected GCA was independent of whether they were GCA-negative or -positive pathologically.The association between GCA and TA infection by VZV was further analyzed by immunohistochemistry in archived TAs of patients with clinically suspected GCA whose TAs were negative histopathologically, and in normal TAs removed postmortem from age-matched subjects21. Serologic evidence shows that more than 95% of the world’s population is exposed to VZV22, and most autopsy studies have found latent VZV DNA in trigeminal ganglia from more than 87% of individuals23. Whereas latent VZV is innocuous, reactivation results in significant disease (see above). Thus, understanding molecular aspects of virus latency is necessary to design therapeutic interventions to inhibit virus reactivation.During primary infection, VZV disseminates hematogenously and infects ganglionic neurons along the entire neuraxis. Neurons may also become infected by retrograde axonal transport of the virus from skin vesicles. In non-neuronal cells, VZV replicates and causes cell death, whereas VZV does not replicate in or kill neurons; rather, transcription of virtually all viral genes is silenced24. Whereas VZV double-stranded DNA is linear in infectious virus particles, VZV DNA is ‘endless’, most likely existing as circular episomes in the nucleus of latently infected neurons25. VZV encodes about 70 genes, all of which are transcribed during productive infection26, but in latently infected human ganglia, only VZV gene 63 RNA is found in the first 9 hours after death27 and fewer than 12 VZV genes are transcribed in the next 15 hours29. Regulation of VZV genes during latency, an active area of research, most likely involves post-translational modification of histone proteins that comprise nucleosomes bound to promoters of virus genes. Nucleosomes containing histone protein 3 (H3) post-transcriptionally modified by acetylation on lysine 9 (K9ac) are present on promoters of actively transcribed cell genes30. Analysis of VZV DNA in human trigeminal ganglia shows that H3K9ac-containing nucleosomes are also present on the promoters of actively transcribed virus genes (VZV genes 21 and 63) but not on virus genes that are transcriptionally silent (VZV genes 14 and 36)31, findings which suggest that latent VZV gene transcription is, in part, regulated epigenetically. Thus, novel therapies that inhibit specific histone modifications may reduce virus reactivation32. Although the initial steps in virus reactivation may involve histone modifications on the latent virus that increase the number of VZV genes transcribed27, the end result of virus reactivation is assembly and release of infectious virions, with extensive cell death and induction of major histocompatibility complex (MHC) class I and II protein with CD4 and CD8 T-cell recruitment35.In latently infected human trigeminal ganglia, one to five copies of VZV DNA are present in 1.5% of the approximately 27,000 neuronsin vitro studies of neurons experimentally infected with VZV offer promise to study mechanisms of VZV reactivation (see below). The immediate future of research on VZV latency will involve correlative analyses of latently infected human ganglia, primate ganglia latently infected with SVV, andin vitro models of neurons experimentally infected with VZV, which can be exploited to prevent serious neurological, ocular, and visceral diseases produced by VZV reactivation.Because VZV is an exclusively human pathogen, studies of VZV latency have been limited to analysis of human ganglia obtained postmortem. However, molecular analysis of latently infected primate ganglia with simian varicella virus (SVV) has provided useful information about varicella latency, and recent36, mice37, and rats38 resulted only in seroconversion. In intradermally inoculated guinea pigs, VZV nucleic acids and proteins were still found in enteric ganglia, stomach, ileum, and colon of guinea pigs 1 month later39. In non-human primates, experimental inoculation of VZV produced a humoral and cell-mediated immune response, but the virus did not become latent in ganglia40.Animal models developed for VZV latency using rodents and primates do not fulfill the criteria for VZV latency, which include detection of VZV DNA exclusively in ganglia, detection of latent VZV only in neurons, restricted transcription of the virus genome, and ability to reactivate the virus. Inoculation of VZV into guinea pigs42, and SVV becomes latent exclusively in ganglionic neurons44. SVV-specific transcription  is limited in ganglia, and the virus can be reactivated by immunosuppression45. SVV antigens are present in macrophages and dendritic cells during reactivation46. Primate models of varicella pathogenesis have revealed that the virus enters ganglia hematogenously before the appearance of skin rash47, memory T cells disseminate SVV to lung and ganglia during primary infection48, and T-cell infiltration correlates with expression of CXCL10, a chemokine that recruits activated T cells and natural killer (NK) cells, in ganglia at the time of zoster49. Pro-inflammatory cytokines and chemokines and anti-inflammatory mediators are elevated at the time of zoster in immunosuppressed monkeys50. All T-cell subsets decreased during immunosuppression and peaked (except for CD8 T cells) 2 weeks before zoster51.However, clinical, virological, immunological, and pathological features of SVV infection in non-human primates closely parallel VZV infection in humans25, viral transcription is severely restricted53, and the virus can reactivate. Anin vitro model of VZV latency that satisfies all three of these conditions has not yet been developed.In latently infected human ganglia, the entire VZV genome is present with termini that are covalently linked )in vitro to a neuron-like cell54. However, differentiation into neurons is inefficient (only approximately 70% are differentiated as determined by phase-contrast microscopy) and infection of the remaining non-neuronal cells leads to productive infection.Neuroblastoma cell lines, including SH-SY5Y, are malignant cell lines of neurogenic origin that can be induced to differentiate56. A cytopathic effect does not develop until about 4 weeks after infection57, whereas similarly infected fibroblasts die in 7 to 10 days. Although this is promising, additional studies are necessary to suppress viral DNA replication, transcription, and virion production to mimic VZV latencyin vivo.Induced pluripotent stem cells (iPSCs) are fibroblasts that have been de-differentiated to a stem cell-like state and then induced to differentiate into neurons. Infection of iPSCs with a low dose of VZV results in a slowly spreading productive infection that produces viral DNA, transcripts, protein, and infectious virusin vitro: neural stem cells (hNSCs) and embryonic stem cells (hESCs). At 9 weeks’ gestation, hNSCs were purified from fetal brain, resulting in approximately 90% neuron purity as indicated by staining for the neuronal markers MAP2a and β-tubulin58. Two weeks after infection with low-dose VZV, no cytopathic effect was evident, although viral DNA, transcripts, and protein were all detectable. hESCs are derived from the inner cell mass ofin vitro fertilized human embryos and can be maintained undifferentiated for at least 8 months in culture59. After differentiationin vitro, VZV infection of hESC-derived neurons results in a lytic infection61. Recently, Markus and colleagues62 claimed to have developed anin vitro model of latency with reactivation of VZV. Although the data in their report do not recapitulate what is known of VZV latency in human ganglia (see above), their model does advance the VZV field since it represents long-term (over a 7-week period), low-level infection, which can be stimulated with various pharmacological agents to boost viral biogenesis .Two other human stem cells have also been used to study the VZV-neuron relationship63. Cells in the TLA express both progenitor and mature neuronal markers and can be maintained for at least 6 months. VZV infection of TLAs results in virus transcription and DNA replication during the initial approximately 18 days of infection, after which a steady-state characterized by persistent infection with sporadic release of virus is reached.Normal human neural progenitor cells can be grown on inert microbeads inside NASA-designed rotary vessels to form tissue-like assemblies (TLAs) that resemble the structure of human ganglia obtained at autopsyin vitro.Overall, the iPSCs, hESCs, and TLA cells have provided prolonged VZV infection of neurons before lytic infection develops but have not produced VZV latency. Further studies involving the use of cytokines, antivirals, and other compounds are needed to possibly achieve latencyIn 1995, varicella vaccine became available in the US. The Centers for Disease Control and Prevention (CDC) recommends immunization at 1 year of age and a second dose at age 4 to 6. Contraindications to the vaccine include life-threatening allergy to previous administration, gelatin or neomycin, pregnancy, and severe immunosuppression. Among states that accurately reported the incidence of varicella, disease declined by 79% overall between 2000 and 2010 and this was likely due to vaccine.64. In that study, 38,546 healthy adults at least 60 years of age (median of 69 years) were randomly assigned to receive a single dose of attenuated VZV with 14-fold higher potency than varicella vaccine or placebo. The higher-potency vaccine was required to increase VZV-specific cell-mediated immunity in latently infected older adults. The incidence of zoster as well as the burden of illness due to zoster  and the incidence of PHN were determined. Average follow-up of 3.13 years in a total of 19,270 people who received zoster vaccine and 19,276 who received placebo revealed 957 confirmed cases of zoster (315 in vaccine recipients and 642 in placebo recipients). In both groups, more than 93% of the subjects with zoster were positive for wild-type VZV DNA by PCR; none had vOka DNA. Zoster vaccine reduced the incidence of zoster by 51.3% (63.9% in people 60 to 69 years old but only 37.6% in people at least 70 years old). The burden of disease was reduced by 61.1% (65.5% in people 60 to 69 years old and 55.4% in people at least 70 years old), and the duration of pain and discomfort among subjects with zoster was shorter in vaccinated candidates compared with placebo recipients. PHN was reduced by more than 65% for both age groups, and the most benefit was in the age group at least 70 years old. The study also showed that vaccination reduced the adverse impact of zoster on patients’ capacity to perform daily life activities and on health-related quality of life.In 2005, the Shingles Prevention Study, a randomized placebo-controlled trial, provided evidence that the herpes zoster vaccine reduced the incidence of zoster and PHN in the elderlyZoster vaccine is safe. Rates of serious adverse events, systemic adverse events, hospitalizations, and deaths were low in vaccine recipients in the study and comparable to those in placebo recipients. During the first 42 days after vaccination, there were 24 cases of zoster in placebo recipients and 7 cases in the vaccination group, but none was caused by vOka. Unlike prophylactic vaccines such as those against varicella and measles, zoster vaccine is a therapeutic vaccine aimed at preventing reactivation of latent VZV in humans already infected before vaccination and thus with substantial immunity.65. Currently, the CDC does not recommend booster doses of zoster vaccine, but may in the future.Zostavax can be given to patients with leukemia, to liver and gastrointestinal transplant recipients, and to patients with HIV infection, but is contraindicated in patients with bone marrow or lymphatic malignancy and patients receiving more than 20 mg/day of prednisone. Zoster vaccine was licensed by the US Food and Drug Administration (FDA) for healthy adults at least 50 years old to prevent zoster and its complications, mainly PHN. Post-licensure studies have confirmed the vaccine’s safety and efficacy. Unfortunately, participation in the zoster vaccine program has been low and this is likely due to cost and failure to recognize the importance of preventing infectious diseases in older adults. The Shingles Prevention Study demonstrated efficacy for 3 years after vaccination, whereas subsequent studies indicated efficacy for 8 years+ T-cell and antibody responses than did vOka67. A randomized placebo-controlled study of 15,411 subjects at least 50 years of age revealed a remarkable 97.2% efficacy in preventing zoster for a 3.2-year period that did not diminish with increasing age68. Systemic adverse reactions were 2.2-fold greater in the vaccine group compared with the placebo group. Because HZ/su does not replicate, it will be safe for immunosuppressed patients. The duration of its effect is unknown. HZ/su vaccine is not yet FDA-approved.Recently, a liposome-based subunit vaccine, HZ/su, containing the VZV glycoprotein E and the adjuvant ASO1B was created. Studies revealed that two doses of HZ/su containing 50 µg of recombinant VZV glycoprotein E administered at 1- or 2-month intervals were well tolerated and induced much more robust VZV-specific and VZV glycoprotein E-specific CD4


Hypoxia plays an important role in tumour recurrence among head and neck cancer patients. The identification and quantification of hypoxic regions are therefore an essential aspect of disease management. Several predictive assays for tumour oxygenation status have been developed in the past with varying degrees of success. To date, functional imaging techniques employing positron emission tomography (PET) have been shown to be an important tool for both pretreatment assessment and tumour response evaluation during therapy. Hypoxia-specific PET markers have been implemented in several clinics to quantify hypoxic tumour subvolumes for dose painting and personalized treatment planning and delivery. Several new radiotracers are under investigation. PET-derived functional parameters and tracer pharmacokinetics serve as valuable input data for computational models aiming at simulating or interpreting PET acquired data, for the purposes of input into treatment planning or radio/chemotherapy response prediction programs. The present paper aims to cover the current status of hypoxia imaging in head and neck cancer together with the justification for the need and the role of computer models based on PET parameters in understanding patient-specific tumour behaviour. References are provided from groups reporting workable solutions to uncertainties arising due to the image acquisition itself; however, as the reports in cers did  and cont2 to cell death probably, that is, radiosensitivity, or cell death to tumour control are nonlinear and dependent on patient specific parameters. The authors remind us that chronic hypoxia remains the focus of the discussed techniques, as opposed to acute/transient hypoxia which may alter in oxygenation faster than the time a PET scan can be acquired and analysed (or radiotherapy planned/delivered). Logistical noteworthy challenges are discussed, for example, the set-up accuracies required, volume expansion protocols for adding margins onto regions of interest nonuniform dose prescription, and how often to rescan during therapy to balance workload of scanning and replanning with the timing of substantial biological change and hence improvement in therapeutic ratio if the plan is altered.This report also discusses the issues of converting oxygenation information into radioresistance estimates and hence prescription requirements, in order to achieve increased tumour control. These are nontrivial challenges, as both functions of converting pOTumour hypoxia remains one of the major causes of treatment failure in head and neck cancer. By promoting angiogenesis as well as distant metastases, hypoxia becomes an important treatment target. In order to increase the therapeutic ratio it is crucial to identify and to quantify the hypoxic subvolumes. To date, PET-based molecular imaging is the most commonly employed technique applied for this purpose.The use of computational models for treatment assessment and prediction is fast growing. Whether simulated or actual PET data has been applied to a tumour response model, overall the current literature suggests that targeting radioresistant hypoxic tumour subvolumes using complex dose gradients or even simpler boost doses is feasible using modern radiotherapy techniques. Research has also shown that toxicity need not be compromised if careful planning is performed, with a possible solution being not to increase the integral dose but rather decrease the prescription to well oxygenated regions and increase it to chronically hypoxic areas. This is still to be confirmed in randomised clinical trials.As it stands currently, all the signs point to hypoxia dose painting as being feasible to tackle notoriously hypoxic tumours, such as head and neck carcinomas. To further improve, the field moves into requiring individual tracer pharmacokinetic information/analysis so that PET data can be accurately interpreted and then utilised appropriately to predict optimal treatment plans and overall outcome improvement.Health institutions will need to encourage and support multidisciplinary research and prioritize resources to make the use of functional PET information feasible, as assessing the dynamic changes of the tumour characteristics at a number of time points after PET injections and then at multiple intervals throughout radiotherapy will always inevitably be highly resource intensive. This will be especially true during the learning phase as this technique is translated from research into the routine clinical environment. Computational pharmacokinetics and tumour models will be vital in this translation process.


To identify the therapeutic effect of the talus control foot orthosis(TCFO) in children with severe flexible flat foot.TCFO is foot orthosis which combines inverted rigid foot orthosis(RFO) with broad upright portion that covers and protects the talonavicular joint, rising well above the navicular.Fourty children were participated in this study who had been diagnosed as flexible pes planus, and had more than two consecutive radiologic studies. The anteroposterior talocalcaneal angles (APTCA) and lateral talocalcaneal angles (LTTCA), the lateral talometatarsal angles (LTTMA) and the calcaneal pitch (CP) of both feet were measured to evaluate foot alignment. Severe flexible pes planus was diagnosed when Beighton hypermobility score was greater than 4 points and when either of the feet had greater than 10 degrees valgus of resting calcaneal stance position angle and indicators showed greater than 55 degrees in APTCA and LTTCA, greater than 10 degrees in LTTMA, lesser than 10 degrees of CP.Twenty children with flexible flat foot were fitted with a pair of RFO and another 20 children were fitted with TCFO. They were recommended to put on orthosis more than 8 hrs a day, to walk with heel strike at initial contact and reciprocal arm swing to normalize gait pattern. The follow up clinical evaluation with radiologic study was done after 12 months.With TCFO, all radiologic indicators changed toward corrective direction than with RFO. There were statistically significant improvements in CP and RCSP in both groups. (p < 0.05) In TCFO group, APTCA, RCSP improved significantly compared with RFO group.This study showed that TCFO is effective in the treatment of children with severe flexible pes planus than RFO. The evaluation with long term follow up of radiographic study would be necessary to confirm the therapeutic effect of TCFO in children with pes planus.


In the Funding section, the grant number for the Science and Technology Development Center, Ministry of Education of the People’s Republic of China grant is missing. The correct grant number is: 20134433120021.


Clostridium clariflavum strain 4-2a, a novel strain isolated from a thermophilic biocompost pile, has demonstrated an extensive capability to utilize both cellulose and hemicellulose under thermophilic anaerobic conditions. Here, we report the draft genome of this strain. Clostridium clariflavum DSM 19732 revealed novel mechanisms among thermophilic clostridia to break down cellulose and hemicellulose (C. clariflavum strain 4-2a is a novel strain isolated from compost (The ability of thermophilic clostridia to extensively degrade lignocellulosic materials and produce fermentation products that may serve as biocommodities makes them excellent candidates for consolidating bioprocessing applications . The genC. clariflavum strain 4-2a was obtained through a phenol-chloroform-CTAB extraction procedure, as previously described (Genomic DNA of escribed  from a shttp://www.jgi.doe.gov. The initial draft data was assembled with ALLPATHS version 39750 (–Protocols for library construction and sequencing performed at the JGI can be found at on 39750  and conton 39750 –10. Gap n 39750 –, and then 39750 –. Genes wn 39750 – and Genen 39750 – as part n 39750 –. Addition 39750 –.C. clariflavum strain 4-2a include the presence of genes coding for xylose isomerase and xylulose kinase in a genomic island not present in the type strain, DSM 19732. The inventory of glycoside hydrolases is almost identical to the one reported for the type strain (Initial findings from the genome of C. clariflavum 4-2a is deposited in GenBank under the accession numbers ASAA01000001 to ASAA01000016 and the annotated genome in IMG through accession number 2524614797.The genome sequence of


The function of the brain depends on the transport of a multitude of fluids, namely blood, cerebrospinal fluid, interstitial fluid and intracellular fluid. Our ability model these intertwined fluid transport processes within brain tissue in an anatomically accurate and patient-specific manner is of ever-increasing significance, especially since integrative systems possess numerous interactions with the external world which either directly or indirectly affect brain function and homeostasis.The current state of knowledge about hydrocephalus (HCP), and more broadly integrative cerebral dynamics and its associated constitutive requirements, advocates that poroelastic theory provides a suitable framework to better understand such a disease. Multiple-network Poroelastic Theory is used to develop a novel spatio-temporal model of tissue displacement and fluid regulation in varying scales within the cerebral environment. The system of equations is discretized in a variety of formats, and in all three spatial dimensions. Both obstructive  and communicating hydrocephalus was investigated in a variety of settings, and accompanied by surgical techniques such as Endoscopic Third and Fourth Ventriculostomy (ETV and EFV). Aquaporin-4 swelling characteristics have also been incorporated into this MPET through the use of simple, functional relationships.Ventriculomegaly, CSF/ISF pressure, wall shear stress and pressure difference between lateral and fourth ventricles increased with applied stenosis, and subsequently dropped to nominal levels with the application of ETV. The greatest reversal of the effects of atresia of the 4th ventricle comes by opting for ETV rather than the more complicated procedure of EFV. Periventricular swelling can also be observed at various stages of HCP development, in both obstructive and communicating HCP simulations.This work presents an assessment of the impact of aqueductal stenosis and 4th ventricle outlet obstruction, along with the applications of ETV and EFV on an anatomically accurate representation of the cerebroventricular system. Theoretical adaptations to communicating HCP were also investigated. Evolution of the MPET model can lead to a level of complexity that could allow for an experimentally guided exploration of areas that would otherwise prove too intricate and intertwined under conventional settings.


Increases in mucosal intestinal permeability may cause pathological leakage of bacterial products, inducing inflammation. Low-grade systemic inflammation has been reported in overweight humans. Probes used for permeability evaluation in humans have not yet been evaluated in dogs.To determine suitability of human permeability probes  for canine obesity models.per os using human doses corrected for weight and reported to be harmless for dogs. Urine samples were collected 2, 4 and 6 h after ingesting probes. Urinary excretion was quantified.Fourteen healthy dogs were examined as baseline group. They were given all four probes The least squares means of mannitol proportion (excreted/ingested ± SE) was 15.6 % (± 2.0), 11.0 % (± 2.1) and 5.5 % (± 2.1) for urine sampled 2, 4 and 6 h after ingestion (p<0.0001). Hence, the majority of mannitol absorption and secretion representing upper gastrointestinal leakage was completed by 4 h. Riboflavin followed a similar temporal profile, defining 4 h as a cutoff for upper vs lower gut permeability. Probes were well tolerated.Data obtained in the study indicates that probes used for humans can be used for intestinal permeability evaluation in dogs.


Previous research has shown that political leanings correlate with various psychological factors. While surveys and experiments provide a rich source of information for political psychology, data from social networks can offer more naturalistic and robust material for analysis. This research investigates psychological differences between individuals of different political orientations on a social networking platform, Twitter. Based on previous findings, we hypothesized that the language used by liberals emphasizes their perception of uniqueness, contains more swear words, more anxiety-related words and more feeling-related words than conservatives’ language. Conversely, we predicted that the language of conservatives emphasizes group membership and contains more references to achievement and religion than liberals’ language. We analysed Twitter timelines of 5,373 followers of three Twitter accounts of the American Democratic and 5,386 followers of three accounts of the Republican parties’ Congressional Organizations. The results support most of the predictions and previous findings, confirming that Twitter behaviour offers valid insights to offline behaviour. Traditionally, psychological differences between liberals and conservatives have been measured with questionnaires and experiments, methods which may suffer from desirability bias and lack of external validity , Republicans used more tentative words than Democrats. One possible interpretation of this result is that, because of the greater need for ambiguity management and cognitive closure in conservatives, they focus on and discuss events with low predictability . PerhapsUsing Twitter as our data source has several limitations which might have affected our findings. Firstly, Twitter messages contain noise; some accounts may be run by institutions, not individuals and may contain deliberately designed content. Secondly, Twitter users are a sample that may not be representative of the general population and the topics discussed on Twitter may not be representative of offline conversation topics. According to a report released by an American think tank, the Pew Research Center, only 14% of the adult population in the US uses Twitter and Twitter users are younger, more educated and more affluent than the population average . ThirdlyLanguage encodes who we are, how we think and what we feel. We show that, even in a noisy Twitter dataset, patterns of language use are consistent with findings obtained through classical psychology methods. With social interactions happening online more and more frequently, social networking platforms are becoming another valid dimension for studying human behaviour. As the field wrestles with questions about experimenter degrees of freedom, self-reporting bias, and replication problems, Big Data approaches such as the one employed here have enormous potential to improve the field’s confidence in its findings. Our research also highlights the difficulty of directly translating psychological constructs to language. Does the fact that we did not find strong effects for some of the previously reported differences mean that they might not be real, that they are real but not expressed in language, or that our method did not capture them? In particular, we struggled with the direction of predictions relating to negativity bias, which raises questions about how certain behavioural characteristics are reflected in language.Our research encourages more investigation into how different social groups express themselves: an interesting extension of this study would be to record how right- and left-leaning proponents speak to see what patterns are present in verbal utterances and how they differ from the patterns found in Twitter messages. Also, by exploring more linguistic categories one might be able to create a more accurate model to predict political orientation. Finally, it would be exciting to investigate how the language of Democrats and Republicans on Twitter changes over time in the context of the 2016 US election. Such research could both enrich current knowledge about the psychology of political ideology and translate into commercial applications.S1 TableMost of the definitions rely on Wikipedia.(DOCX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.


Furrow irrigation proceeds under several soil-water-furrow hydraulics interaction dynamics. The soil erosion consequences from such interactions in furrow irrigation in Samaru had remained uncertain. A furrow irrigation-induced erosion (FIIE) model was used to simulate the potential severity of soil erosion in irrigated furrows due to interactive effects of infiltration rates, land slope, and some furrow irrigation characteristics under different scenarios. The furrow irrigation characteristics considered were furrow lengths, widths, and stream sizes. The model itself was developed using the dimensional analysis approach. The scenarios studied were the interactive effects of furrow lengths, furrow widths, and slopes steepness; infiltration rates and furrow lengths; and stream sizes, furrow lengths, and slopes steepness on potential furrow irrigation-induced erosion, respectively. The severity of FIIE was found to relate somewhat linearly with slope and stream size, and inversely with furrow lengths and furrow width. The worst soil erosion (378.05 t/ha/yr) was found as a result of the interactive effects of 0.65 m furrow width, 50 m furrow length, and 0.25% slope steepness; and the least soil erosion (0.013 t/ha/yr) was induced by the combined effects of 0.5 l/s, 200 m furrow length, and 0.05% slope steepness. Evidently considering longer furrows in furrow irrigation designs would be a better alternative of averting excessive FIIE. The use of mathematical models and computer simulations in engineering, hydrology, and various fields in the process of decision making is progressively gaining more acceptances . Models Furrow irrigation is one of the most conventionally practiced irrigation methods in the area. About 60% of irrigated lands in Nigeria are furrow-irrigated . Furrow Erosion problems are complex owing to a combination of socioeconomic factors and common agricultural practices. A wide range of locally and internationally funded research projects from the government, nongovernmental organizations (NGOs), and the academia have addressed rainfall erosion problems in Samaru, for example, the works of Adewumi , Adewumi discharge measurements which are the basis of FIIE assessment are commonly used to calculate the average soil loss per unit field area (Mg/ha) . However, from a practical viewpoint, erosion rates on a field vary widely with many soil and furrow hydraulic factors. For example, erosion and sediment transport capacity increase with the shear or velocity of the flow, which in turn increase with the flow rate and furrow slope. Further, 50 to 80% of a typical furrow inflow infiltrates before it reaches the furrow end, resulting in a corresponding flow rate decrease along the furrows [The furrows . UnderstNicetic et al.  showed tField experiments were conducted during the 2009/2010 and 2010/2011 irrigation seasons at the Irrigation Research Field of the Institute for Agricultural Research (IAR) farm, Samaru, Zaria, along the Zaria-Sokoto road . Samaru is situated within the Northern Guinea savanna zone of Nigeria.Q, furrow length L, and furrow widths W at 3, 2, and 2 levels, respectively. The stream sizes were 2.5, 1.5, and 0.5 l/s; furrow lengths were 90 and 45 m; and furrow widths were 0.75 and 0.9 m. The combination of the stream sizes, furrow length, and furrow widths resulted in twelve (12) different treatments that were imposed on the field as follows: Q1, Q2, and Q3 are stream sizes 2.5, 1.5, and 0.5 l/s, respectively; L1 and L2 are furrow lengths 90 and 45 m, respectively; W1 and W2 are furrow widths 0.75 and 0.9 m. The layout of the experiment was a randomized complete block laid in a split plot design with four replications. This layout was observed in both 2009/2010  and 2010/2011  seasons. Main plots consisted of stream sizes while furrow lengths and furrow widths were focused in the subplots. In both of the study seasons, each replication comprised three plots, and each experimental plot had three and two ridges in Trials 1 and 2, respectively.The experimental factors studied were stream size K, was determined by adopting the universal soil loss equation (USLE) “K” equation as it is in Wall et al. [The basic infiltration rate of the soil was determined using the inflow-outflow method. Slope of the field was determined in each of the two trials using the dumpy level surveying instrument. The hydraulic shear stress τ was obtained following the guidance of Schwab et al. . The soil et al. . The timPrior to commencement of irrigations, water-sediment collection stations were established 5 m before the end of each furrow. Flow of water in the furrows was measured using a cutthroat flume installed 5 m from entry at the upstream and at the tail end of the furrows for the measurement of water inflow and outflow of the furrows. Water flowing out of the furrows was measured as runoff. One liter of water-sediment samples was collected during irrigation events at each of the established measurement points and was taken to laboratory and filtered into preweighed metal containers. The resultant residues were oven-dried at 105°C over 24-hour period and reweighed. Sediment concentrations (g/L) were calculated from the dried residues and the runoff volumes for each of the treatments and were used to calculate soil erosion per furrow. Runoff volume was calculated as the product of the runoff discharge (l/s) (from the downstream flumes) and duration of runoff discharge. Soil erosion at the end of the furrows was calculated as the product of the sediment concentrations and runoff volumes divided by the wetted area. The wetted area was calculated as the product of the top width of flow of water and the length of the furrow , 18–20.π-theorem considering the variables in The furrow irrigation-induced erosion (FIIE) model was developed using dimensional analysis approach following the concept of Buckingham π-theorem require that the variables to be used in the dimensional analysis be theoretically independent. Some of the variables in  of 0.941. The model was found to be most sensitive to stream size and least sensitive to time of flow of water in the furrows.A two-year field experiment was embarked upon to collect data for the completion of the model development. Five accuracy . The effSoil erosion in irrigated furrow is practically a function of many variables, among which only stream sizes, furrow length, and width were studied, and it is often not possible to monitor the influence of every land-use practice under all weather and soil conditions. Scientific planning for soil conservation and water management requires knowledge of the relations among those parameters that cause the soil erosion . These pScenario 1: Effects of Furrow Lengths, Furrow Widths, and Slopes Steepness on Potential Furrow Irrigation-Induced Erosion. According to Savva and Frenken [S in furrow irrigation. Frenken , the wid Frenken . Low irrScenario 2: Effect of Combined Infiltration Rates and Furrow Lengths on Potential Furrow Irrigation-Induced Erosion. A number of soil factors affect farm irrigation system selection. Among other factors, soil texture plays a vital role through its effect on the available soil moisture and, most importantly, the infiltration rate of the soil. Many shallow soils, often with a depth of no more than 30 cm, are commonly developed for irrigation in many regions. At times, such soils may be of light texture obliging very frequent irrigation. The infiltration rate affects the length of run, size of furrows, and the application rates. Within the same soil textural group, infiltration rate can vary considerably, for instance, 20 to 30 and 5 to 10 mm/hr for sandy loam and clay loam soils, respectively [ectively . IrrigatScenario 3: Effects of Combination of Stream Sizes, Furrow Lengths, and Field Slopes on Potential Furrow Irrigation-Induced Erosion. In irrigation practice, the use of very small stream size, Q, prolongs infiltration opportunity time (I.O.T.) and causes deep percolation at the upstream end of the furrow if the bottom end is also to receive enough water. On the other hand, the use of very large stream size speeds up the waterfront and reduces I.O.T.; this leads to high runoff losses and erosion hazards in the furrows. Apparently, the selection of appropriate combinations of stream sizes Q and furrow length L is necessary. The I.O.T. can be regulated in irrigated furrow to avert over- or underirrigation and its corresponding negative implications. Practically, this has not been of any concern to farmers despite its necessity in achieving good irrigation efficiency and averting erosion hazards. Water application can be regulated by increasing or decreasing the I.O.T. One can, within limits, regulate the depth of water applied. One method of achieving this is by decreasing the I.O.T. by steepening the slope S and shortening the furrow length L or by increasing the stream flow. In this method, one factor is varied while two other factors remain unchanged. But what is the magnitude of erosion problem associated with the combination of any factors mentioned? This scenario addresses it. In this analysis, three stream sizes , four furrow lengths , and four slope steepness values  were selected as representatives of what is commonly found in farmers' farm. For every value of Q, a corresponding value of d and t was measured from the field during the experiment and the values of τ were computed therefrom. The model was then used to generate the potential soil erosion values for every combination of Q, L, and S. The predicted FIIE as consequent combinations of furrow lengths and various infiltration rates is presented in Similarly, the prediction shows another decreasing trend of soil erosion at a particular furrow length with increase in infiltration rate. For example, soil erosion dropped by about 33% in any particular furrow length between infiltration rates of 20 to 30 mm/hr. Often many irrigated fields, especially large farms, could have more than one type of soils or some slight spatial variation in the composition of the soil, hence varying in infiltration rates. The table supplies the irrigator with estimate possible of soil erosion that could be incurred and could be useful for planning irrigation.The prediction also called for prudence to be exercised when selecting large stream sizes to irrigate short furrows on steep slopes. When it is necessary to irrigate steep furrows, smaller stream size in a longer length of run is a better and safer option as pointed out in the table. The information in Tables 3 through 5 would serve as guide for the determination of optimum combinations of furrow lengths, widths, and stream sizes under varied slope and infiltration rates.Models are employed in the systematic analysis of complex causal relationships to simulate the reactions and interactions of different variables to be able to identify inexplicit causal relationships of variables and their consequences. The FIIE model was herein used to explore the soil erosion consequences of the combinations of field slope, furrow lengths, top width of flow, infiltration rates, and stream sizes at various scales during furrow irrigation. The result stressed the danger of irrigating on steep slopped lands, cautioned against irrigation in short furrows, and called for prudent selection of flow stream sizes to circumvent severe soil erosion during furrow irrigation. Conducting such visualizations on a routine basis will help in providing a roadmap towards realization of sustainable irrigated agriculture.


From the frozen-in field lines concept, a highly conducting fluid can move freely along, but not traverse to, magnetic field lines. We discuss this topic and find that in the study of the frozen-in field lines concept, the effects of inductive and capacitive reactance have been omitted. When admitted, the relationships among the motional electromotive field, the induced electric field, the eddy electric current, and the magnetic field becomes clearer. We emphasize the importance of isomagnetic surfaces and polarization charges, and show analytically that whether a conducting fluid can freely traverse magnetic field lines or not depends solely on the magnetic gradient along the path of the fluid. If a fluid does not change its density distribution and shape (can be regarded as a quasi-rigid body) and moves along isomagnetic surface, it can freely traverse magnetic field lines without any magnetic drag, no matter how strong the magnetic field is. Besides theoretical analysis, we also present experimental results to support our analysis. The main purpose of this work is to correct a fallacy among some astrophysicists. The concept of frozen-in magnetic field originated from Alfvén  is oftenIt has been established by Bellan that under certain conditions, a highly conducting fluid can freely cross magnetic field lines . Here weFor convenience, the term “fluid” used in the following means an ideal conducting fluid.The magnetic flux through a fluid is conserved (we designate this definition “conservation theorem”).Any motion of the fluid perpendicular to the field lines carries the field lines with the fluid (we designate this definition “frozen theorem”). This frozen theorem is often presented in another form: “a fluid cannot freely traverse magnetic field lines.”Although the concept of frozen-in field lines is often used by some authors, it currently lacks a specific definition. The following two definitions are familiar to many readers.Magnetic flux can be conserved in both scenarios:All field lines within a fluid move along with the fluid.The number of field lines entering a given fluid equals that leaving it at any instant.Hence the two theorems are actually not equivalent. We accept the conservation theorem but question the frozen theorem.Under the conditions that the external magnetic body and its magnetic field are stationary, if a fluid moves perpendicularly to the field lines, the field lines must bend and exert a resistive force on the fluid.The magnitude of the resistive force exerted on the fluid depends on the magnetic field strength. The stronger the magnetic field, the greater the resistive force.There is a corollary to the frozen theorem: At low beta where the magnetic field is strong and produced by external coils, one pictures the fluid being pushed around by the magnetic field , while at high beta where the magnetic field is weak, one pictures the fluid pushing the magnetic field around. In either case, the magnetic field and the fluid move together. Note that this corollary and the frozen theorem include two notions:It is indisputable that in most cases when a fluid traverses a magnetic field, a resistive force will be exerted on the fluid. However, this does not mean that the traverse motion must result in the appearance of magnetic drag. In this paper, we seek those special conditions under which a fluid can freely traverse magnetic field without any magnetic drag, no matter how strong the magnetic field is.u is the relative velocity of the fluid element moving through the magnetic field B, and u × B is the motional electromotive field. The frozen theorem follows from the evolution equation of the magnetic field From For any spatial position passed by a fluid, the magnetic evolution depends on the crossing motion of the fluid. Without crossing motion, there must be no magnetic evolution; andu × B ≠ 0, as long as ∇ × (u × B) = 0, there must be no magnetic evolution.Even a fluid crosses a magnetic field, namely u × B ≠ 0, the magnetic evolution and magnetic drag can be absent as long as the condition ∇ × (u × B) = 0 is satisfied.This indicates that field-line crossing is a necessary, but not sufficient, condition for magnetic evolution. The magnetic evolution arising from the motion of the fluid always co-exists with magnetic drag and neither phenomenon can appear alone, because both arise from one and the same eddy current. Therefore, field-line crossing is also a necessary but not sufficient condition for magnetic drag. In other words, even if fluid crosses a magnetic field, i.e. u × B. When both sides of u.It is known that the essential condition for a force acting between the fluid and the magnetic field is the presence of an eddy current within the fluid, whereas the essential condition for the presence of eddy current is the presence of an eddy motional electromotive field ∇ ⋅ B, which, according to Maxwell’s equation, is always zero.Now, the purpose to determine the condition under which a fluid can freely traverse magnetic field without magnetic drag turns into another one to determine the condition under which both sides of ∇ ⋅ u in the second term is the divergence of the velocity field. If the density distribution of the fluid remains constant, this term also equals zero.The factor u ⋅ ∇)B vanishes.When each fluid element moves along an isomagnetic surface, the third term (B ⋅ ∇)u vanishes too. In general, the differential movement is related to a change in shape of the fluid.If the fluid elements that synchronously cross the same magnetic field line have the same velocity , the fourth term , no magnetic force acts on the fluid. However, if the differential rotation can be described as ω = f(z) , a magnetic force will act on the fluid. This distinction arises from the fourth term of the right-hand side of ω = f(r), then (B ⋅ ∇)u = 0 and no magnetic force appears; if ω = f(z), then (B ⋅ ∇)u ≠ 0 and a magnetic drag will appear. This result is consistent with the law of iso-rotation (Ferraro’s theorem) which states that in the steady state, angular velocity is constant along magnetic lines [ω = f(r), the angular velocity varies only along the direction perpendicular to the field lines. In this situation, although the fluid is no longer quasi-rigid because of the appearance of differential rotation, it can still traverse magnetic field lines freely. This indicates that the constraint condition of “quasi-rigid” can be softened to a certain extent.For the case shown in ic lines . If ω = Alfvén & Fälthammar has described an example similar to that in Because the case shown in Figs If a magnetic field changes in the direction of fluid movement, the fluid will generally experience drag. In particular, if the length of fluid along the direction of its motion is greater than the extent of the magnetic field, magnetic drag is inevitable at the magnetic boundary because the magnetic field changes sharply and the magnetic gradient is very high there.Now, it has been clear that when a quasi-rigid fluid crosses a uniform magnetic field, the system is always force-free, no matter what velocity the fluid is moving with and how strong the magnetic field is. On the other hand, every steady magnetic field can be regarded as a superposition of uniform and non-uniform components and only the non-uniform component may, not must, result in magnetic drag. From this perspective, we can clearly understand the interaction between fluid and magnetic field and avoid to be misled by the frozen theorem.The following equation describes the distribution of polarization charges inside the fluid:elittled  even diselittled . This mi-∇·(u×B).In MHD lelittled  and knowelittled . Second,This demonstrates that in some cases, the electrical neutrality approximation must be abandoned and the effects of the electric field and charges must be considered.According to conventional physics, a straight wire, closed wire or conducting plate see  moving pE  shown in Figs E that produces a fluid drift and “thaws” the magnetic-frozen states. A simple calculation using the drift theory of charged particles [E and B is always equal to the macroscopic moving velocity of the fluid, i.e., vdrift = (E × B)/B2 ≡ u [In previous studies on the frozen-in effect, the effects of the polarization charges and electrostatic field articles  verifies/B2 ≡ u , 19.B and a static electric field E, with E perpendicular to B, will freely drift across the magnetic field lines. Based on Bellan’s viewpoint, we claim that the static electric field E, which is established by polarization charges, can naturally appear under certain conditions. The process by which this can occur is summarized below:Bellan  has demou × B inside the fluid;A fluid moving across the magnetic field lines induces an irrotational motional electromotive field As a result of this irrotational motional electromotive field, polarization charges appear inside the fluid or its boundaries;E = −u × B;The polarization charges result in a static polarization electric field, and the motional electromotive field is balanced by the polarization electric field, E combines with B to “force” all the particles (ions and electrons) to drift with velocity vdrift equal to u. Namely, the velocity of the guiding-center drift equal to the motion velocity of the fluid.Finally, the system is force-free and the fluid can move freely as the magnetic field is absent.When an individual charged particle travels through a magnetic field, it is subject to Lorentz forces which compel it to gyrate around the magnetic field lines. However, within a fluid, the presence of both polarization charges and electric field create a very different situation. Under some special conditions, such as those illustrated in Figs In the situations shown in Figs There is an opinion in some books –7 whose Because the conductivity of ideal conducting fluid is infinite, if the induced electric field appears inside the fluid, the induced current must be infinite. Hence the induced electric field cannot appear inside the ideal conducting fluid.I = V/R or J = σE) was incorrectly used to the non-steady or open circuit system.Their opinion is incorrect and the root of this mistake is that the Ohm’s law  that controls the current growth. This law is also valid in MHD field because the electric field, current, and magnetic field are generally time-variant. It is similar that in the DC circuit, only resistance is considered, but for the AC circuit, the reactance must be considered. Below, we show how the inductive reactance and capacitive reactance restrain the current growth and why the fluid can traverse magnetic field lines.u × B must appear to drive a current to grow. At the same time, an induced electric field E immediately appears to restrain the current growth and makes the current always finite. The relation between them is E = −u × B. Since the motional electromotive field u × B has two components, rotational and irrotational components, the induced electric field E has two components too.When a fluid traverses magnetic field lines, a motional electromotive field ∇ × (u × B). The opposite component of the induced electric field is ∇ × E = −∂B/∂t. This induced electric field component is caused by the time-variant magnetic field. The time-variant magnetic field is caused by the time-variant eddy current and this eddy current is caused by the rotational motional electromotive field. As long as the direction of ∇ × (u × B) does not reverse, the eddy current will grow continually. But the rate of growth depends on the inductive reactance. In a real system, the magnetic field caused by the eddy current only offsets the change of the external magnetic field along the motion path and conserves the magnetic flux; so the eddy current must be finite unless the external magnetic field can become infinitely strong. From that, it is the inductive reactance that restrain the eddy current to be always finite inside the ideal conducting fluid.The rotational component of the motional electromotive field is When a rotational electric field appears inside an ideal conducting fluid, the system must be evolutive. The Ohm’s law cannot be used in such non-steady system.∇ ⋅ (u × B) and the opposite component of induced electric field is ∇ ⋅ E = q/ϵ0. This induced electric field component is caused by the polarization charges and the polarization is driven by the irrotational motional electromotive field. As long as a fluid traverses a magnetic field, this irrotational component of the induced electric field is always non-zero as shown in Figs The irrotational component of the motional electromotive field is E and the motional electromotive field (u × B) are still nonzero.However, the boundary conditions can affect the irrotational current. In the cases shown in Figs E+(u × B) = 0; but it is wrong to think always E = 0 and u × B = 0. When taking the inductive and capacitive reactances into account, we can understand why E ≠ 0 and u × B ≠ 0 would not result in an infinite current inside ideal conducting fluid.Inside the conducting fluid  and q = ϵ0∇ ⋅ (u × B) will be meaningless.From the above analyses, we can get following logical relation: If a fluid cannot traverse magnetic field lines, the motional electromotive field All in all, the non-zero motional electromotive field caused by the fluid’s traversing motion is the root of the system evolution and would not result in an infinite current. Supposing that the fluid freezes with the field lines and deny the field-line crossing, we will actually deny the system evolution. Therefore we have to accept the concept that a conducting fluid can traverse magnetic field lines. The field-line crossing is not only acceptable but also indispensable.We have discussed that the fluid elements can freely cross magnetic field lines in the cases of the uniform magnetic field and quasi-rigid fluids. Other researchers , howeverIn previous discussions on the frozen theorem, attention has usually been devoted to only the fluid and the magnetic field lines inside the fluid. However, as long as the system studied is extended to also include the external magnet and the magnetic field lines outside the fluid see , we willu relative to the magnet, as shown in First, we assume that the magnetic field is uniform, the magnet is immobile and the quasi-rigid fluid moves with velocity In any field-lines passing through fluid will be cut off by fluid’s crossing motion. Apparently, this solution is also unacceptable.In In If the field lines outside the fluid respond to the fluid motion, only three possible solutions can be considered, as illustrated in Some problems arisen from the misuse of the concept of moving field lines have been discussed by other researchers , 22. WitWe suggest using a better method to describe the relationship between moving fluid and magnetic field lines. When a fluid crosses a magnetic field along the isomagnetic surface, we can consider that the field lines are stationary with the magnet and the fluid crosses them freely. If a fluid crosses a non-uniform magnetic field along the direction of magnetic gradient, as shown in The magnetic drag is, in fact, the force acting between the external magnet and the fluidic magnet. Although the forces acting on the front and rear sides of the fluid are always opposite, the magnetic gradient makes their magnitudes different. No matter what direction the fluid is moving, parallel or opposite to the magnetic gradient, the result of the forces is always opposite to the motion direction.When the two magnetic fields are combined to form one field, 1 in 1 instead of pulled from P0, because these dashed magnetic field lines had not appeared when the fluid was at P0. Therefore, this two-magnet interpretation needs neither frozen-in field lines nor moving field lines.A notable point is that the dashed field lines at PUnder the condition that the fluid is a quasi-rigid body, this two-magnet interpretation infers the following:When a fluid crosses magnetic field lines, eddy current can appear inside the fluid.The eddy current turns the fluid into a fluidic magnet and causes an additional magnetic field to appear.Because the two-magnets interact with each other, the magnetic drag appears.The additional magnetic field always counteracts changes in magnetic flux caused by the external magnet and conserves the total flux inside the fluid.The additional magnetic field will change the magnetic configuration outside the fluid.Because the eddy current depends on the magnetic gradient, the effects above disappear outright if the fluid moves along the isomagnetic surface.Using the two-magnet interpretation, we can clearly understand not only the magnetic conservation inside the fluid but also the magnetic variation outside the fluid.The concept of magnetic reconnection has no longer been needed, even on the fluid boundary.The problems shown in Since this two-magnet interpretation emphasizes that the eddy current depends on the magnetic gradient, the importance of the isomagnetic surface become easier to understand.Since this two-magnet interpretation emphasizes the field-lines crossing, it comes clear that the fluid motion causes the volume density distribution of the polarization charges.Compared with the frozen theorem, this two-magnet interpretation has the following strengths:0 to P1, the field lines to the left of P1 grow denser instead of sparser. If the frozen theorem holds and field lines have been carried by the fluid from P0 to P1, the field lines there must become sparser and are similar to Note that this interpretation is very different with the frozen theorem. As shown in In For clarity, the analysis results of Eqs  and 3)  3) are sThe frozen theorem was expressed in several forms, which are summarized in To verify the special significance of isomagnetic surface, we conducted a series of magnetohydrodynamic experiments. The configuration of the device is the same as that of aligned magnetic rotator, a cylindrically symmetric magnet whose magnetic axis aligns with its rotation axis. The three experiments are as follows:Drive experiment A [riment A . RevealeDrive experiment B [riment B . RevealeDrive experiment C [riment C . RevealeThe experiments were divided into two groups. The first group comprised three pairs of experiments to determine the conditions under which the magnet can drive rotation of the mercury. In each experiment the basis of comparison is an The first group of experiments demonstrated that an aligned magnetic rotator cannot drive the mercury to rotate. However, this result has not proved the absence of the magnetic frozen effect in such cases, since this result can be attributed to another cause: the magnetic field lines don’t co-rotate with the aligned magnetic rotator. When a magnet rotates around its own magnetic axis, whether the magnetic field corotates with the magnet has been a controversial issue. This issue is also named as Faraday paradox. Although most of astrophysicists think the magnetic field corotates with the magnet, we take the opposite point of view because it is accepted by the most of general physical scientists and supported by more experiments for Faraday paradox.Fälthammar once pointed that field lines are not tangible objects that move in the normal sense. One cannot distinguish the axisymmetric field of a cylindrical magnet rotating about its axis from the field of a non-rotating magnet and so one cannot assign a rotation to the magnetic field lines . Backus The value of these experiments is to answer the question: Can an aligned pulsar drive its plasma and achieve the co-rotation state? The answer is NO.aligned magnet, a cylindrically symmetric magnet whose magnetic axis matched that of the mercury rotation axis. In this case, the mercury eventually revolved at the same rate as the trough. For the three comparison cases, braking forces reduced the rotation of the mercury. We used the same magnets in every pair of braking experiments, designated A, B and C and described below.Braking experiment A [riment A . RevealeBraking experiment B [riment B . RevealeBraking experiment C [riment C . RevealeIn the second group of experiments, the conditions under which rotating mercury can be slowed by a stationary magnet were determined. The mercury trough  was spun until the mercury revolution reached a steady state. In each experiment the basis of comparison was an The braking experiments demonstrated that even if the magnetic field is non-uniform, fluid can experience no frozen-in effect, as long as all of the fluid elements move along isomagnetic surface. Thereby, the analyses for These experimental results have verified the special significance of isomagnetic surface: Along isomagnetic surface, a magnetic field can neither drive nor brake conducting fluid.B are also moved. There is no way to make sense, in general, out of the idea of ‘the speed of a moving field line.’”Our ideas are embodied in the following quote from Feynman et al. : “It makIn fact, a magnetic field essentially cannot be ascribed a movement. Time-varying magnetic fields exist, whereas moving ones do not. While it can be intuitive and useful to regard magnetic field lines as moving, this approach is often unsafe as discussed by Fälthammar & Mozer .In conventional physics, certain electromagnetic problems have been correctly solved by assuming moving field lines. But in those situations, the magnetic poles always move with the field lines. By contrast, typical discourses on the frozen theorem did not clarify whether the magnetic source body is in motion or at rest. If the external magnet is at rest , the assumption that the field lines are movable always makes the physics more complex and even leads to wrong results. Herein lies the root of the problem caused by the frozen theorem.For some astrophysical objects, the magnetic field may be very strong, but the magnetic gradient in the direction of the plasma movement is usually very small, especially for the cases similar to that shown in Magnetic confinement technology has been widely applied in nuclear fusion engineering. In those devices, plasma is restrained in the magnetic beam and cannot move laterally. One interpretation for this phenomenon is that the very strong magnetic field restrains the plasma. Actually, it is the transverse magnetic gradient that does the restraining, especially near the boundary surface of the magnetic beam. Any uniform magnetic field, regardless of strength, cannot restrain a conductive substance. But some people think that at low beta where the magnetic field is strong, the fluid will be pushed around by the magnetic field lines and if the field is stationary, so is the fluid. The reason why some people think so may be that they were misled by the frozen theorem.When the magnetic evolution and magnetic drag are the study objects, the electrical neutrality is indeed an excellent approximation. However, when the drift of fluid particles and fluid’s crossing motion are concerned, we must pay more attention to the electric field and the charges distribution. In the latter case the electrical neutrality approximation is unacceptable.Whether a quasi-rigid conducting fluid can freely traverse magnetic field lines or not depends solely on the magnetic gradient along the fluid path. No matter how strong the magnetic field is or how fast the fluid speed is, a fluid can freely traverse the magnetic field lines as long as it moves along the isomagnetic surface. Especially, no matter how strong the magnetic field is, a uniform magnetic field cannot push around conducting fluid.The literal meaning of “frozen-in” is liable to promote an erroneous association between fluid traversing motion and magnetic drag. Therefore, we suggest that the use of this term should be avoided whenever possible. In particular, the frozen theorem should not be used to study MHD problems.


Today Show, US Representative Michele Bachmann claimed that human papillomavirus (HPV) vaccines could cause “mental retardation”.New media changes the dissemination of public health information and misinformation. During a guest appearance on the The purpose of this study is to explore how new media influences the type of public health information users access, as well as the impact to these platforms after a major controversy. Specifically, this study aims to examine the similarities and differences in the dissemination of news articles related to the HPV vaccination between Google News and Twitter, as well as how the content of news changed after Michele Bachmann’s controversial comment.This study used a purposive sampling to draw the first 100 news articles that appeared on Google News and the first 100 articles that appeared on Twitter from August 1-October 31, 2011. Article tone, source, topics, concerns, references, publication date, and interactive features were coded. The intercoder reliability had a total agreement of .90.P<.001), duration (P=.005), vaccine eligibility for females (P=.03), and protection against diseases (P=.04) than did the later pieces. After the controversy, the news topic shifted towards politics (P=.01) and talked more about HPV vaccine eligibility for males (P=.01).Results indicate that 44.0% of the articles (88/200) about the HPV vaccination had a positive tone, 32.5% (65/200) maintained a neutral tone, while 23.5% (47/200) presented a negative tone. Protection against diseases 82.0% (164/200), vaccine eligibility for females 75.5% (151/200), and side effects 59.0% (118/200) were the top three topics covered by these articles. Google News and Twitter articles significantly differed in article tone, source, topics, concerns covered, types of sources referenced in the article, and uses of interactive features. Most notably, topic focus changed from public health information towards political conversation after Bachmann’s comment. Before the comment, the HPV vaccine news talked more often about vaccine dosing (This longitudinal infodemiology study suggests that new media influences public health communication, knowledge transaction, and poses potential problems in the amount of misinformation disseminated during public health campaigns. In addition, the study calls for more research to adopt an infodemiology approach to explore relationships between online information supply and public health decisions. The dissemination of health communication has undergone dramatic changes as digital distribution and social media transfer considerable power to users and enhance opportunities for asynchronous mass delivery. According to the Pew Internet & American Life Project , 72% of HPV represents one of the most common sexually transmitted infections linked to cancer. Researchers found that an underestimated 93% of invasive cervical cancers worldwide contain HPV . The FooToday Show on September 13, 2011, after criticizing Texas Governor Rick Perry, GOP Presidential candidate, for mandating HPV vaccines for school girls, Bachmann claimed that a crying woman had recently approached her and said that her daughter received the HPV vaccine and consequently developed “mental retardation” [While health professionals argue for stronger public health campaigns to promote the HPV vaccination, communication efforts have been challenged on political platforms by US Representative Michele Bachmann. During a guest appearance on the rdation” . The AmeThe distribution of this type of public health misinformation is unclear and proves especially difficult to track due to unlimited diverse online news sources and the ability of social media users to participate and negotiate the information-exchange process. Public health specialists suggest that new media, such as social networking sites and online news aggregators, may have the potential to impact the public’s understandings and their adoption decisions of the HPV vaccination ,5. ThereEysenbach ,8 suggesThe Centers for Disease Control (CDC) reports that as of June 2011, more than 35 million doses of the HPV vaccination had been distributed in the United States. Nonetheless, the introduction of HPV vaccination has come with its own unique set of challenges. One key challenge in the promotion of the HPV vaccination program is the recommended age of immunization. The recommendation is to vaccinate young girls prior to sexual debut, with the recommendation of ages starting at 11-12 years . AdditioNew technologies allow greater opportunities for difficult-to-reach patients to receive health information and make personal health care decisions . HoweverMany scholars have examined the news coverage of the HPV vaccination when it was first released ,11,14-17While scholars provided important insights on how media first disseminate information related to the HPV vaccination, little scholarly attention has been given to social media dissemination reports, which could be crucial to the vaccination promotion today.This type of follow-up research becomes even more necessary when additional news surrounding the vaccination has little to do with the public health initiative itself. For example, in September 2011, US Representative Michele Bachmann brought the side effects of the HPV vaccines into the political discussion. Her controversial comment that HPV vaccination could cause mental retardation soon fueled online debate between scientific, political, and family communities ,14,18. EWhile it is challenging to examine how much influence this type of public health misinformation has on personal health care decisions, it is valuable to investigate information shared through online public forums. “Although few would argue that spreading blatant misinformation should be a punishable offense, false claims about vaccine risk can have deadly consequences when they discourage vaccination” . This caThe purpose of this study is to compare aggregated news stories shared on Google News and retweets shared on Twitter both before and after Bachmann’s comment to help understand the public health information dissemination through both social media and news aggregates. A snapshot of the Google News search criteria is illustrated in RQ1: What are the similarities and differences in the HPV vaccination coverage between Google News and Twitter?Today Show?RQ2: How did the content of news articles centered on the HPV vaccination change after Bachmann’s 2011 interview on the Google News and Twitter are among the primary sources that researchers use to study news media and information dissemination -21. GoogTwitter, on the other hand, is a social media site that provides information, news, and communication about what users are interested in ,25. On TWhile it may be argued that the structure and purpose of news dissemination on Twitter differs from that on Google News, it is appropriate to analyze and compare articles disseminated through both platforms. Social media research demonstrates how Twitter is being used primarily as a resource for individuals to access and communicate on recent news issues ,20. FurtGoogle News Archive database was used to identify Google News articles on HPV vaccination from August 1-October 31, 2011. The 3-month time period was chosen because it includes 1.5 months before and 1.5 months after Bachmann’s comment about the HPV vaccines on September 13, 2011. In addition, a 3-month period is a common timeframe used by content analysis studies on information dissemination ,27. TopsA purposive sampling was used to draw the first 100 news articles that appeared on the Google News search results pages and the first 100 news articles that appeared on the Topsy search results pages. This represents a sample that audiences are likely to access and read, as previous research suggests that users typically start from the top of search results/tweets and read only the first few pages of search results/tweets ,29. DuplEach news article was coded for seven key variables: (1) date , (2) tone of the article , (3) article source , (4) topics covered in the article , (5) concerns raised in the article , (6) types of sources referenced in the article , and (7) interactivity . All the coding categories are based on previous literature ,31.Two researchers carried out the coding independently. Coders were trained using a preliminary subset of news stories. The training process continued until the coders were comfortable with the various coding categories . DetaileApproximately 20% of the total sample was randomly selected to assess intercoder reliability, including news articles disseminated by both Google News and Twitter. A Cohen’s kappa test was run on all seven variables that required a judgment call from the coders. The measure of agreement was as follows: date=1.0, tone of the article=.85, article source=.98, topics covered in the article=.90, concerns raised in the article=.80, types of sources referenced in the article=.78, and interactivity=1.0. The total agreement was .90, which indicates a high level of reliability on the coding instrument and across coders.A total of 100 Google News articles and 100 Twitter articles were coded to examine the similarities and differences in information gathering and diffusion of HPV vaccination. Overall, 37.5% articles (75/200) were published before Bachmann’s comment, and 62.5% (125/200) appeared after her interview. Specifically, among the 100 articles from Google News, 45.0% (45/100) were published before Bachmann’s comment, and 55.0% (55/100) were after. Among the Twitter articles coded in this study, 30.0% (30/100) were published before Bachmann’s interview, while 70.0% (70/100) were after.Among the news articles analyzed in this study, 44.0% (88/200) had a positive tone towards HPV vaccination, 32.5% (65/200) a neutral tone, and 23.5% (47/200) presented a negative tone. The top three topics covered by these articles were protection against diseases , vaccine eligibility for females , and side effects . Safety , mandatory school vaccination , and age concern  were the most frequently mentioned concerns related to the vaccine. In addition, CDC  was the most-cited reference in these articles, followed closely by the research community , and medical doctors . Most of the news articles disseminated by Google News and Twitter were newspaper/magazine articles , articles appearing on health organizations’ websites , and user-generated content . Furthermore, this analysis found that increased interactivity became a trend during this public health dialogue. The majority of the news articles coded in this study included more than one type of interactive feature, such as hyperlinks and search functions.22=8.895, P=.01; see To answer RQ1, this study found that Google News and Twitter articles significantly differed in tone, source, topics, concerns raised, types of sources referenced, and uses of interactive features. First, results indicate that news articles presented by Google News and linked to Twitter presented different tones when diffusing information about the HPV vaccination. Among the Twitter articles coded in this study, 54.0% (54/100) had a positive tone, 29.0% (29/100) a neutral tone, while only 17.0% (17/100) had a negative tone. On the other hand, Google News had an equal distribution in terms of the article tone towards HPV vaccination, that is, positive , neutral , negative . The chi-square test result was significant , protection against diseases , side effects , and vaccine efficacy . Specifically, Google News articles covered topics of vaccine eligibility for females, protection against diseases, and vaccine efficacy significantly more frequently than its Twitter counterparts. On the contrary, news articles linked to Twitter-reported topics around politics and side effects significantly more often than did Google News. No statistically significant differences were found in coverage about vaccine cost, duration, dosing, and eligibility for males between news articles disseminated by Google News and Twitter. Protection against diseases  was the most frequently covered topic by Google News, followed by vaccine eligibility for females  and vaccine efficacy . The top three topics for Twitter articles were protection against diseases , side effects , and vaccine eligibility for females .In addition, this study found that Google News and Twitter were significantly different in their coverage about vaccine eligibility for females . No statistically significant differences were found regarding any other concerns coded in this study. Safety , mandatory school vaccination , and age concerns  were the most frequently mentioned concerns regarding the HPV vaccination in Google News articles. Similarly, safety , mandatory school vaccination , and affordability  were the top three concerns raised by articles linked to Twitter.Vaccine accessibility was the only concern expressed significantly differently between Google News and Twitter articles. Articles linked to Twitter addressed the accessibility of the HPV vaccination more frequently than did Google News , medical doctors , and political and government officials/organizations  as reference sources significantly more often than its Google counterparts; while Google News cited the research community more frequently than did Twitter . No statistically significant differences were found in the quotations from CDC, vaccine manufacturers, and cancer organizations. CDC , medical doctors , and political officials  were the most frequently used references in Twitter articles, while the research community  was the major reference for Google News articles, followed by CDC . It is also important to note that while 31.0% (31/100) of the Twitter articles used personal accounts as a reference source, only 8.0% (8/100) of the articles from Google News did the same.As shown in 28=39.997, P<.001; see Moreover, newspapers/magazines , user-generated content , and health organizations’ websites  were the top three sources for articles linked to Twitter, while newspapers/magazines , health organizations’ websites , and scientific journals  were the major sources for Google News articles. Interestingly, while 4.0% (4/100) of the Twitter articles used government websites as the source to disseminate information about the HPV vaccines, zero Google News articles came from government websites. While 28.0% (28/100) of the Twitter articles about the vaccination came from user-generated content, only one Google News article  used this source. The chi-square test suggests a significant difference in article source used by Google News and Twitter .While this study found that both articles from Google News and those linked to Twitter encouraged the interactivity between content providers and consumers during this public dialogue about HPV vaccination, significantly more Twitter articles allowed users to leave comments, compared to its Google News counterparts , duration , vaccine eligibility for females , and protection against diseases  significantly more often than did the later pieces. After Bachmann’s Today Show appearance, not surprisingly, the news topics shifted towards politics , and interestingly, news articles talked about HPV vaccine eligibility for males more frequently .To answer RQ2, this study tests the similarities and differences in news articles regarding HPV vaccination before and after Michele Bachmann’s 21=13.789, P<.001), duration , eligibility for females , and protection against diseases  significantly more often before Bachmann’s interview than did the later pieces. Nonetheless, after Bachmann’s Today Show appearance, Twitter linked to more HPV news articles focused on politics than before . It is important to note that this study found no significant topic changes in Google News articles before and after Bachmann’s comment.Specifically, Twitter articles covered information regarding the HPV vaccine dosing . However, no statistically significant differences were found in uses of other types of reference sources in these articles before and after the controversy. The top three reference sources used before Bachmann’s comment were CDC , the research community , and medical doctors ; while afterwards, the top three were CDC , the research community , and political and government officials/organizations .In addition, this study found that the articles focused on HPV vaccination used cancer organizations as a reference source significantly more often after Bachmann’s comment than before . Nonetheless, Twitter articles used government and political officials/organizations as reference sources significantly more frequently after Bachmann’s comment than before . In terms of concerns raised in these HPV vaccine news, Twitter articles expressed concerns related to accessibility of the vaccine  and the importance of continued Pap smears  significantly more often before the comment than the later pieces. Articles from Google News mentioned concerns related to mandatory school vaccination significantly more before Bachmann’s Today Show appearance than its later pieces . This study did not find significant differences in terms of article tone, interactivity, and article source between news disseminated before and after Bachmann’s comment.Specifically, Google News articles cited cancer organizations significantly more often after Bachmann’s comment than before , this result is consistent with expectations. Nonetheless, findings suggest that Twitter took on the role of a “soap box” for users to voice outrage against Bachmann’s misinformed comment after her appearance on the This research also compared how Bachmann’s controversial comment impacted the online public dialogue about the HPV vaccination. Interestingly, the study found no differences in overall article tones, concerns raised by the news and reference sources used before and after her appearance. According to our research, topic change was the only major shift happened after Bachmann’s comment. Results indicate a turn towards a political discussion after Bachmann’s comment. Fewer news articles talked about the important treatment information about the HPV vaccines, such as vaccine dosing, duration, and protection against diseases after the controversy. This finding demonstrates that misinformation not only pushed forth an increase in articles that contained false public health information, but transformed dialogue from a public health initiative to a political debate.It is important to note that the content of news articles disseminated through Twitter were highly impacted by Bachmann’s misinformed comment while Google News articles remained more consistent. After the controversy, Twitter had many more articles related to politics, while Google News was able to maintain the same or even increased the amount of articles centered on the science and the vaccine itself. This finding is interesting, as it points to a key difference between a strictly news aggregate (Google News) search and an aggregator within a social media platform (Twitter). While Twitter does allow for users to “retweet” news stories that they find in other users’ feeds, they are also given the option to add on to these conversations with their own viewpoints or experiences. This suggests that Twitter provides a structure that allows for users to lead public dialogue in any direction that they choose, or in this case, politics. Google News, however, served as more of a top-down dissemination of “expert” information. While there are certainly opportunities and challenges of each of these structures, in regards to misinformation, Twitter allows for users to fight back against, or increase the spread of, misinformation. This proves a much more egalitarian medium, as the everyday user is able to trend the same manner as an expert.Today Show and immediately became concerned about HPV vaccines causing mental retardation, they would likely share that concern with their social network so that they could become informed and engage in dialogue. If their physician was a part of their online social network, he or she could also add to the conversation and help facilitate the dialogue by filtering out misinformation.If more physicians utilized Twitter and/or other social media  as a platform to both disseminate and gather news with their patients, more could be done to minimize the misinformation shared, without diluting the participatory process for individual users. For example, if an individual heard Bachmann’s comment on the Although this research provides valuable insights into the dissemination of public health information via new media, it is important to note the limitations of a content analysis study. This research cannot provide accurate insights into the influence or effect that this dissemination has on users. In addition, this research examined only the top news that appeared on Twitter and Google News. Future studies may consider examining all articles within the timeframe. Nonetheless, such a purposive sample (instead of studying the entire population or drawing a probability sample) represents a practical frame of the articles audiences read, which can be more valuable when seeking an understanding of how public opinion is formed. Moreover, this study focused on the news articles 1.5 months before and 1.5 months after Bachmann’s comment, which captures the short-term differences between Twitter and Google News coverage. Future research may consider gathering data within a longer timeframe to better understand how online sources impact public opinion about important health issues.Overall, this infodemiology study suggests that new media is influencing public health communication and the patient’s role in today’s dynamic communication environment ,33. Whil